Search

Abstract Background In clinical practice, alterations in the internal environment of type 2 diabetes can significantly affect bone quality. While the increased risk of fractures among diabetic patients is well-established, the precise mechanisms by which hyperglycemia influences bone quality remain largely unclear. Methods Western blotting, immunohistochemistry (IHC), and micro-CT were used to examine ferroptosis-related protein expression and bone morphology changes in the bone tissues of type 2 diabetic mice. The CCK8 assay determined the optimal conditions for inducing ferroptosis in osteoblasts by high glucose and high fat (HGHF). Ferroptosis phenotypes in osteoblasts were analyzed using flow cytometry, Western blotting, and two-photon laser confocal microscopy. Transcriptomic sequencing of the control and HGHF groups, followed by bioinformatic analysis, identified and validated key genes. TIMP1 was knocked down in osteoblasts to assess its impact on ferroptosis, while TFRC expression was inhibited and activated to verify the role of TIMP1 in regulating ferroptosis through TFRC. The therapeutic effect of TIMP1 inhibition on osteoporosis was evaluated in a type 2 diabetic mouse model. Results The expression of TIMP1 is increased in type 2 diabetic osteoporosis. In vitro, TIMP1 knockout inhibited ferroptosis in osteoblasts induced by high glucose and high fat (HGHF). However, overexpression of TFRC reversed the ferroptosis inhibition caused by TIMP1 knockout. Suppression of TIMP1 expression alleviated the progression of osteoporosis in type 2 diabetic mice. Mechanistic studies suggest that TIMP1 regulates HGHF-induced ferroptosis in osteoblasts through TFRC. Conclusion This study demonstrates that TIMP1 expression is increased during type 2 diabetic osteoporosis and that TIMP1 promotes ferroptosis in osteoblasts by regulating TFRC. These findings suggest that TIMP1 is a promising novel therapeutic target for type 2 diabetic osteoporosis.

Abstract Low fluid shear stress (FSS, ≤ 2 dyn/cm2) has been shown to exert protective effects on chondrocytes, but the underlying molecular mechanisms remain unclear. This study aimed to elucidate the mechanisms by which FSS promotes chondrocyte proliferation and extracellular matrix (ECM) stability. We exposed SW1353 chondrocytes to low FSS (1.8 dyn/cm2, 60 min) and found that it led to a significant downregulation of microRNA-143-3p (miR-143-3p), which was associated with increased chondrocyte proliferation and ECM secretion, including type II collagen (COL2A1) and aggrecan. Further investigation revealed that miR-143-3p directly targeted ERK5, a key component of the ERK5/KLF4 signaling pathway. Overexpression of miR-143-3p suppressed ERK5/KLF4 pathway activation, resulting in reduced chondrocyte proliferation and ECM production. Our findings demonstrate that low FSS promotes chondrocyte proliferation and ECM secretion by downregulating miR-143-3p, leading to the activation of the ERK5/KLF4 signaling pathway. This study reveals a novel mechanism by which FSS regulates chondrocyte behavior and ECM secretion, highlighting the potential of FSS as a therapeutic target for cartilage-related diseases.

Abstract Objective This study investigated the protective effects of low fluid shear stress (FSS ≤ 2 dyn/cm²) against interleukin-1β (IL-1β)-induced chondrocyte apoptosis and explored the underlying molecular mechanisms. Methods Chondrocytes were cultured under four conditions: control, IL-1β stimulation, low FSS, and combined low FSS + IL-1β stimulation. Apoptosis was assessed using Hoechst staining and flow cytometry. Western blotting determined the expression of caspase-3 (CASP3), caspase-8 (CASP8), and NF-κB p65. Quantitative real-time PCR measured miR-143-3p expression. The roles of miR-143-3p and the extracellular signal-regulated kinase 5 (ERK5)/Krüppel-like factor 4 (KLF4) signaling pathway were further investigated using miR-143-3p mimics and inhibitors, an ERK5 inhibitor, and a KLF4 overexpression vector. Results IL-1β induced significant chondrocyte apoptosis, which was markedly inhibited by low FSS. Mechanistically, low FSS suppressed miR-143-3p expression, thereby enhancing ERK5 signaling. This activated ERK5 subsequently upregulated KLF4 expression, further mitigating IL-1β-induced damage. Importantly, miR-143-3p overexpression under low FSS conditions exacerbated IL-1β-induced apoptosis, while miR-143-3p inhibition attenuated it. Consistent with this, ERK5 inhibition augmented IL-1β-induced apoptosis, whereas KLF4 overexpression suppressed it. Conclusion Low FSS protects chondrocytes from IL-1β-induced apoptosis by suppressing miR-143-3p and activating the ERK5/KLF4 signaling pathway. This study reveals a novel mechanism by which mechanical stimulation protects cartilage.

Abstract Articular cartilage damage and wear can result in cartilage degeneration, ultimately culminating in osteoarthritis. Current surgical interventions offer limited capacity for cartilage tissue regeneration and offer only temporary alleviation of symptoms. Tissue engineering strategies are increasingly recognized as promising modalities for cartilage restoration. Currently, various biological scaffolds utilizing tissue engineering materials are extensively employed in both fundamental and clinical investigations of cartilage repair. In order to optimize the cartilage repair ability of tissue engineering scaffolds, researchers not only optimize the structure and properties of scaffolds from the perspective of materials science and manufacturing technology to enhance their histocompatibility, but also adopt strategies such as loading cells, cytokines, and drugs to promote cartilage formation. This review provides an overview of contemporary tissue engineering strategies employed in cartilage repair, as well as a synthesis of existing preclinical and clinical research. Furthermore, the obstacles faced in the translation of tissue engineering strategies to clinical practice are discussed, offering valuable guidance for researchers seeking to address these challenges.

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: “Graft Selection” and “Clinical Outcome Evaluation” during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive “gold standard” graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

Objective: This study aimed to investigate the effects of swimming exercise on cartilage, inflammatory markers, subchondral bone structure, and stride length in mice with knee osteoarthritis induced by anterior cruciate ligament (ACL) transection, and to explore the role of miR-143-3p in these effects. Methods: Thirty-six 3-month-old male C57BL/6 mice were randomly divided into three groups: control, exercise (swimming 30 min daily for one month), and exercise + miR-143-3p mimics (swimming exercise plus intra-articular injection of miR-143-3p mimics lentivirus once every two weeks for four weeks). Experimental groups underwent ACL transection to induce osteoarthritis. Interventions began two weeks post-modeling. Post-intervention, stride length analysis, histological analysis (including assessment of cartilage morphology and chondrocyte number), and micro-CT scanning (to assess subchondral bone structure) were performed. Inflammatory markers were measured in cartilage. Results: Swimming exercise partially alleviated joint inflammation (as evidenced by reduced levels of IL-1β), protected cartilage (maintaining chondrocyte number and extracellular matrix homeostasis, as demonstrated by improved cartilage morphology), and enhanced subchondral bone structure. However, miR-143-3p supplementation partially inhibited these beneficial effects of swimming exercise. Both exercise groups showed gait impairment (reduced stride length) compared to controls, with no significant difference between the two exercise groups. Conclusion: Swimming exercise can mitigate osteoarthritis progression by protecting cartilage, improving subchondral bone structure, and reducing inflammation. However, miR-143-3p partially counteracts these protective effects.

Objective This study aimed to compare infection, aseptic loosening, revision, operation time, function scores, and the radiographic radiolucent line (RLL) between cementless and cemented fixation in total knee arthroplasty (TKA). Methods Articles reporting the outcomes of cemented and cementless TKA were searched in Medline, EMBASE, Web of Science, and the Cochrane Library. The search was conducted from articles published from January 1996 to May 2024. Odds Ratios (OR) and confidence intervals (CI) were used to measure the results. Cochrane Collaboration’s Review Manager software was used to perform the meta-analysis. Results Sixteen randomized controlled trials containing 2358 participants were included in this meta-analysis. Pooled data found that, in TKA, there were no significant differences between cemented fixation and cementless fixation for a prosthesis in infection, aseptic loosening and revision. The subgroup analysis and sensitivity analysis results of the knee society score (KSS) showed a significant difference favoring cementless fixation in a follow-up of less than 5 years (MD = −2.30, 95%CI –3.85 -0.74, p = .001) while favoring cemented fixation in a follow-up over 5 years (MD = 2.79, 95%CI 0.95 4.63, p = .003). The operation time of cementless was less than that of cemented (MD = 12.03, 95%CI 8.30 15.77, p < .00001). No significant difference was detected in knee society function score, Western Ontario and McMaster Universities osteoarthritis index, and RLL. There was no heterogeneity across studies ( p > .1), and most studies have a low risk of bias. Conclusions Within a follow-up period of less than 5 years, cementless TKA had better KSS, while over 5 years, KSS was better in cemented TKA, and cementless TKA required less operation time.

Double-bundle (DB) anterior cruciate ligament (ACL) reconstruction has biomechanical advantages over single-bundle reconstruction. However, most studies perform the DB reconstruction with 2 femoral tunnels, which fails to provide an entire femoral footprint for ACL reconstruction. In this study, we describe a femoral double-bundle footprint technique for ACL reconstruction, named the tendon groove technique. This technique modifies the DB femoral tunnels through connecting 2 inner orifices of the anteromedial bundle and the posterolateral bundle tunnels, creating a groove to ensure an entire ACL footprint. This modified technique achieves an anatomic and double-bundle ACL reconstruction with a native footprint, which increases the tendon-bone interface area and theoretically promotes tendon-bone healing in ACL reconstruction.

Objectives Multiple ligament knee injuries (MLKIs) are disruptive injuries, however, there are controversies in the results of acute and delayed reconstruction. Also, clinical outcomes between patients older or younger than 40 have not been compared in MLKIs. This study was designed to investigate the influence of age and timing of reconstruction on the outcomes of single‐stage reconstruction of MLKIs. Methods The patients who underwent reconstruction of multiple injured ligaments because of MLKIs between May 2013 and July 2019 were added to the cohort. The postoperative complications, knee range of motion (ROM), Lysholm score, International Knee Documentation Committee (IKDC) 2000 score, Tegner activity level, patient satisfaction, and SF‐36 score were compared between young (≤ 40 years old, n = 41) and old patients (n = 61); acute (≤ 3 weeks after injury, n = 75) and delayed reconstruction (n = 27), using Mann–Whitney U test or χ2 test. Results A total of 102 MLKI patients managed by single‐stage multi‐ligament reconstruction were retrospectively reviewed. Patients were followed up after surgery for a mean of 7.3 years (5.2‐10.7 years). At the last follow‐up, no significant difference was found in knee ROM, functional scores, and patient‐reported outcomes between patients older or younger than 40; acute and delayed reconstruction (p > 0.05). The rate of complications in the delayed reconstruction group was higher than that of the acute reconstruction group (22.2% vs 5.3%, p

This study explores the role of disulfidptosis in monocytes and its relation to postmenopausal osteoporosis (PMOP). Using single-cell RNA sequencing and microarray assays, we identified key genes: LONRF1, ACAP2, IPO9, and PGRMC2. Through differential analysis, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning, these genes were linked to PMOP. Functional enrichment and ROC curve analysis demonstrated their effectiveness in distinguishing postmenopausal fracture patients from healthy individuals. Notably, PGRMC2 exhibited significant expression differences, highlighted by a notable Area Under the Curve (AUC) value of 0.665. Further investigation involved Western blotting and immunohistochemical assays, revealing decreased PGRMC2 expression in ovariectomized (OVX) mice. This decrease was consistent across both experimental methods, emphasizing PGRMC2's role in PMOP. Moreover, PGRMC2 was predominantly present in macrophages compared to monocytes within bone tissue and was significantly located in bone marrow mesenchymal stem cells (BM-MSCs) in PMOP patients. It was also abundantly found in osteoblasts and adipocytes. Additionally, a Mendelian randomization analysis using the TwoSampleMR R package, with data from decode and GWAS databases, was conducted. This analysis showed a significant impact of PGRMC2 on osteoporosis risk (p = 0.0048, OR = 0.6836), suggesting a potential protective effect against the disease. Our results suggest that PGRMC2 may facilitate the differentiation of monocytes into macrophages in bone tissue, influencing the behavior of BM-MSCs. This, in turn, could impact the progression and severity of PMOP. The study provides new insights into the molecular mechanisms underlying postmenopausal osteoporosis and highlights the potential of PGRMC2 as a therapeutic target or biomarker for this condition.

Abstract Senile osteoporosis is mainly caused by osteoblasts attenuation, which results in reduced bone mass and disrupted bone remodeling. Numerous studies have focused on the regulatory role of m6A modification in osteoporosis; however, most of the studies have investigated the differentiation of bone marrow mesenchymal stem cells (BMSCs), while the direct regulatory mechanism of m6A on osteoblasts remains unknown. This study revealed that the progression of senile osteoporosis is closely related to the downregulation of m6A modification and methyltransferase-like 3 (METTL3). Overexpression of METTL3 inhibits osteoblast aging. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that METTL3 upregulates the stability of Hspa1a mRNA, thereby inhibiting osteoblast aging. Moreover, the results demonstrated that METTL3 enhances the stability of Hspa1a mRNA via m6A modification to regulate osteoblast aging. Notably, YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) participates in stabilizing Hspa1a mRNA in the METTL3-mediated m6A modification process, rather than the well-known degradation function. Mechanistically, METTL3 increases the stability of Hspa1a mRNA in a YTHDF2-dependent manner to inhibit osteoblast aging. Our results confirmed the significant role of METTL3 in osteoblast aging and suggested that METTL3 could be a potential therapeutic target for senile osteoporosis.

Osteoporosis (OP) is a widespread age-related disorder marked by decreased bone density and increased fracture risk, presenting a significant public health challenge. Central to the development and progression of OP is the dysregulation of the mechanistic target of the rapamycin (mTOR)-signaling pathway, which plays a critical role in cellular processes including autophagy, growth, and proliferation. The mTOR-autophagy axis is emerging as a promising therapeutic target due to its regulatory capacity in bone metabolism and homeostasis. This review aims to (1) elucidate the role of mTOR signaling in bone metabolism and its dysregulation in OP, (2) explore the interplay between mTOR and autophagy in the context of bone cell activity, and (3) assess the therapeutic potential of targeting the mTOR pathway with modulators as innovative strategies for OP treatment. By examining the interactions among autophagy, mTOR, and OP, including insights from various types of OP and the impact on different bone cells, this review underscores the complexity of mTOR’s role in bone health. Despite advances, significant gaps remain in understanding the detailed mechanisms of mTOR’s effects on autophagy and bone cell function, highlighting the need for comprehensive clinical trials to establish the efficacy and safety of mTOR inhibitors in OP management. Future research directions include clarifying mTOR’s molecular interactions with bone metabolism and investigating the combined benefits of mTOR modulation with other therapeutic approaches. Addressing these challenges is crucial for developing more effective treatments and improving outcomes for individuals with OP, thereby unveiling the therapeutic potentials of targeting the mTOR-autophagy axis in this prevalent disease.

BackgroundPostmenopausal osteoporosis is a prevalent disease that affects the bone health of middle-aged and elderly women. The link between gut microbiota and bone health, known as the gut-bone axis, has garnered widespread attention.MethodsWe employed a two-sample Mendelian randomization approach to assess the associations between gut microbiota with osteoclasts and postmenopausal osteoporosis, respectively. Single nucleotide polymorphisms associated with the composition of gut microbiota were used as instrumental variables. By analyzing large-scale multi-ethnic GWAS data from the international MiBioGen consortium, and combining data from the eQTLGen consortium and the GEFOS consortium, we identified microbiota related to osteoclasts and postmenopausal osteoporosis. Key genes were further identified through MAGMA analysis, and validation was performed using single-cell data GSE147287.ResultsThe outcomes of this study have uncovered significant associations within the gut microbiome community, particularly with the Burkholderiales order, which correlates with both an increase in osteoclasts and a reduced risk of postmenopausal osteoporosis. with an odds ratio (OR) of 0.400, and a P-value of 0.011. Further analysis using single-cell data allowed us to identify two key genes, FMNL2 and SRBD1, that are closely linked to both osteoclasts and osteoporosis.ConclusionThis study utilizing Mendelian randomization and single-cell data analysis, provides new evidence of a causal relationship between gut microbiota and osteoclasts, as well as postmenopausal osteoporosis. It was discovered that the specific microbial group, the Burkholderiales order, significantly impacts both osteoporosis and osteoclasts. Additionally, key genes FMNL2 and SRBD1 were identified, offering new therapeutic strategies for the treatment of postmenopausal osteoporosis.

Abstract Purpose The purpose of the study was to summarize the available evidence and identify risk factors for osteochondral injuries (OCIs) after patellar dislocations. Methods A systematic literature review was conducted in PubMed, Embase, Web of Science, Cochrane Library, and China national knowledge infrastructure from inception to December 22, 2022, according to the preferred reporting items for systematic reviews and meta-analyses guidelines. Studies regarding risk factors for OCIs after patellar dislocations were included. Literature search, data extraction, and quality assessment were performed independently by two authors. Results A total of 16 studies with 1945 patients were included. The risk factors for OCIs after patellar dislocation were categorized into four main categories, including demographic characteristics, patellar depth and position, femoral trochlear morphology, and other risk factors in this study. Five and three studies supported the idea that male sex and skeletal maturation may be risk factors, respectively. Normal femoral trochlea (two studies) and complete medial patellofemoral ligament (MPFL) injuries (two studies) may be associated with the development of OCIs. Three studies show that ligamentous laxity or joint hypermobility may prevent OCIs. Patellar depth and position (eight studies) may not be associated with the development of OCIs. Conclusions Based on the available evidence, an increased risk of OCIs following patellar dislocation may be associated with male sex and skeletal maturation. Furthermore, normal femoral trochlea and complete MPFL injuries may increase the risk of OCIs, while factors such as ligamentous laxity or joint hypermobility may reduce the risk. Level of Evidence Level IV, systematic review of Level II and IV studies.

Osteoporosis (OP) is a common metabolic bone disease characterized by low bone mass, decreased bone mineral density, and degradation of bone tissue microarchitecture. However, our understanding of the mechanisms of bone remodeling and factors affecting bone mass remains incomplete. Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase that regulates a variety of cellular metabolisms, including inflammation, tumorigenesis, and bone metabolism. Recent studies have emphasized the important role of SIRT1 in bone homeostasis. This article reviews the role of SIRT1 in bone metabolism and OP and also discusses therapeutic strategies and future research directions for targeting SIRT1.

Bones are vital for anchoring muscles, tendons, and ligaments, serving as a fundamental element of the human skeletal structure. However, our understanding of bone development mechanisms and the maintenance of bone homeostasis is still limited. Extracellular signal-related kinase 5 (ERK5), a recently identified member of the mitogen-activated protein kinase (MAPK) family, plays a critical role in the pathogenesis and progression of various diseases, especially neoplasms. Recent studies have highlighted ERK5’s significant role in both bone development and bone-associated pathologies. This review offers a detailed examination of the latest research on ERK5 in different tissues and diseases, with a particular focus on its implications for bone health. It also examines therapeutic strategies and future research avenues targeting ERK5.

Objective In order to reduce the “killer turn” effect, various tibial tunnels have been developed. However, few studies investigated the biomechanical effects of different tibial tunnels during PCL reconstruction. This study aims to compare the time‐zero biomechanical properties of anteromedial, anterolateral, lower anteromedial, and lower anterolateral tibial tunnels in transtibial posterior cruciate ligament (PCL) reconstruction under load‐to‐failure loading. Methods Porcine tibias and bovine extensor tendons were used to simulate in vitro transtibial PCL reconstruction. Forty bovine extensor tendons and 40 porcine tibias were randomly divided into four experimental groups: anteromedial tunnel group (AM group, n = 10), anterolateral tunnel group (AL group, n = 10), lower anteromedial tunnel group (L‐AM group, n = 10), and lower anterolateral tunnel group (L‐AL group, n = 10). The biomechanical test was then carried out in each group using the load‐to‐failure test. The ultimate load (in newtons), yield load (in newtons), tensile stiffness (in newtons per millimeter), load‐elongation curve, failure mode, and tibial tunnel length (in millimeter) were recorded for each specimen. One‐way analysis of variance (ANOVA) was used to compare the mean differences among the four groups. Results The biomechanical outcomes showed that there were no differences in the mean tensile stiffness and failure mode among four groups. The ultimate load and yield load of the L‐AM group were significantly higher than those of other three groups (P 0.05). There was significant statistical difference in the length of tibial tunnel between anatomic groups (AM and AL) and lower groups (L‐AM and L‐AL) (P

Objective Percutaneous suture is a classic technique used in Achilles tendon repair. However, the complication rates surrounding the sural nerve remain relatively high. Modified percutaneous repair technology can effectively avoid these complications; however, the surgical procedure is complicated. Hence, the present study was conducted to describe a redesigned repair technique for the Achilles tendon able to avoid sural nerve injury and reduce the complexity of the procedure. Methods Data of patients with acute primary Achilles tendon rupture at our hospital from January 2019 to May 2020 were included. Subjects with expectations for surgical scarring underwent a minimally invasive‐combined percutaneous puncture technique. The surgical time, requirement for conversion to other technologies, and length of postoperative hospitalization were investigated to assess efficacy. The American Orthopedic Foot & Ankle Society (AOFAS) score and the Arner–Lindholm scale (A‐L scale) were used to assess postoperative clinical outcomes (> 24 months). During the 2‐year follow‐up, MRI was performed to observe the healing of the Achilles tendon. In addition, subjective satisfaction with surgical scar healing was recorded. Results Twenty consecutive subjects with an average follow‐up of 28.3 ± 4.5 months (range, 24–41) met the inclusion criteria. None of the 20 enrolled patients required a converted surgical approach. The mean surgical time was 26.9 ± 6.47 min (range, 20–44). None of the patients experienced dysesthesia or anesthesia around the sural nerve. No signs of postoperative infections were observed. MRI data showed that the wounds of the Achilles tendon healed completely in all the subjects. The AOFAS score increased from 55.6 ± 11.07 (range, 28–71) preoperatively to 97.8 ± 3.34 (range, 87–100) at the last follow‐up. The A‐L scale showed that 90% of the subjects (n = 18) presented as excellent and 10% of the subjects (n = 2) presented as good, with an excellent/good rate of 100%. Moreover, subjects' satisfaction for surgical scars was 9.1 ± 0.78 (upper limit, 10). Conclusions The results indicate that this technique can achieve good postoperative function, a small surgical incision, and high scar satisfaction. In addition, this technique should be widely used in suturing Achilles tendon ruptures.

Abstract Background This study aimed to investigate the association between sleep duration and bone mineral density (BMD) and determine whether vitamin D (VD) status influenced the association between sleep duration and BMD. Methods National Health and Nutrition Examination Survey 2007–2014 participants aged ≥ 40 years were included in this study. BMD testing was conducted with dual-energy X-ray absorptiometry examinations. Moreover, all individuals were divided into four groups according to self-reported nocturnal sleep duration (7–8 h; 6 h; 8 h). In addition, the differences in BMD between the normal sleep duration group and other groups were calculated using multiple linear regression models. Results Overall, the median age of the overall study population was 55.00 years old, with 46.97% of men distributed. Participants sleeping > 8 h/night had lower BMDs than those sleeping 7–8 h/night. Moreover, the association between unhealthy sleep duration (especially > 8 h/night) and low BMD was more pronounced in older individuals, men, postmenopausal women, and subjects with inadequate VD intakes ( 60 years, men, or postmenopausal women. Moreover, VD status might influence the association between sleep duration and BMD, especially in the context of inadequate VD intake or deficient/insufficient serum 25-hydroxyvitamin D levels. However, given the limitations of the present study, further investigation is warranted to confirm this association and to explore potential mechanisms.

Piezo1, a mechanosensitive ion channel, participates in a variety of biological processes in maintaining bone homeostasis. As the most abundant cells in bones of the mammals, osteocytes play an essential role in bone formation, remodeling, and bone mass maintenance. Here, by exposing MLO-Y4 osteocytes to the fluid shear stress (FSS) microenvironment, we explored the effect of Piezo1-mediated FSS on the expression of the molecules critical to the process of bone formation and resorption, Receptor Activator of Nuclear Factor-Kappa-B Ligand (RANKL) and Osteoprotegerin (OPG). It was found that 9 dyne/cm2 loading for 30 minutes showed an upregulation trend on Piezo1 when MLO-Y4 osteocytes were exposed to an FSS microenvironment. FSS promotes the expression of OPG and inhibits the expression of RANKL. The blocker of Piezo1, GsMTx4, downregulates the effect of FSS on the expression of these two molecules. In addition, NOTCH3 was involved in this process. Thus, the results demonstrated that Piezo1-mediated FSS promotes the expression of OPG and inhibits the expression of RANKL via NOTCH3 in MLO-Y4 osteocytes.

Osteoarthritis (OA) is a debilitating joint disorder that affects millions of people worldwide. Despite its prevalence, our understanding of the underlying mechanisms remains incomplete. In recent years, transient receptor potential vanilloid (TRPV) channels have emerged as key players in OA pathogenesis. This review provides an in-depth exploration of the role of the TRPV pathway in OA, encompassing its involvement in pain perception, inflammation, and mechanotransduction. Furthermore, we discuss the latest research findings, potential therapeutic strategies, and future directions in the field, shedding light on the multifaceted nature of TRPV channels in OA.

Objective During the transtibial posterior cruciate ligament (PCL) reconstruction, surgeons commonly pay more attention to the graft turning angle in the sagittal plane (GASP), but the graft turning angle in the coronal plane (GACP) is always neglected. This study hypothesized that the three‐dimensional (3D) killer turn angle was determined by both the GASP and GACP, and aimed to quantitively analyze the effects of the GASP and GACP on the 3D killer turn angle. Methods This was an in‐vitro computer simulation study of transtibial PCL reconstruction using 3D knee models. Patients with knee injuries who were CT scanned were selected from the CT database (April 2019 to January 2021) at a local hospital for reviewing. A total of 60 3D knees were simulated based on the knees' CT data. The femoral and tibial PCL attachment were located on the 3D knee model using the Rhinoceros software. The tibial tunnels were simulated based on different GASP and GACP. The effects of the GASP and GACP on the 3D killer turn angle were quantitatively analyzed. One‐way analysis of variance was used to compare the outcomes in different groups. The regression analysis was performed to identify variables of the GASP and GACP which significantly affected 3D killer turn angle. Results The 3D killer turn angle showed a significant proportional relationship not only with the GASP (r2 > 0.868, P 0.467, P

Abstract Objective To investigate the association between different body fat distribution and different sites of BMD in male and female populations. Methods Use the National Health and Nutrition Examination Survey (NHANES) datasets to select participants. The weighted linear regression model investigated the difference in body fat and Bone Mineral Density (BMD) in different gender. Multivariate adjusted smoothing curve-fitting and multiple linear regression models were used to explore whether an association existed between body fat distribution and BMD. Last, a subgroup analysis was performed according to age and gender group. Results Overall, 2881 participants were included in this study. Compared to males, female participants had lower BMD (P

Objective To determine the permissive safe angle (PSA) of the tibial tunnel in transtibial posterior cruciate ligament (PCL) reconstruction based on a three‐dimensional (3D) simulation study. Methods This was a computer simulation study of transtibial PCL reconstruction using 3D knee models. CT images of 90 normal knee joints from 2017 to 2020 were collected in this study, and 3D knee models were established based on CT data. The tunnel approaches were subdivided into the anterior 1/3 of the anteromedial tibia (T1), middle 1/2 of the anteromedial tibia (T2), the tibial crest (T3), anterior 1/3 of the anterolateral tibia (T4), middle 1/2 of the anterolateral tibia (T5). Five tibial tunnels (T1–T5) were simulated on the 3D knee models. The PSAs, in different tibial tunnel approaches were measured, and subgroup analyses of sex, age and height were also carried out. Results The mean PSAs of the tibial tunnels with 5 different approaches (T1–T5) were 58.49° ± 6.82°, 61.14° ± 6.69°, 56.12° ± 7.53°, 52.01° ± 8.89° and 49.90° ± 10.53°, respectively. The differences of the mean PSAs between the anteromedial and anterolateral approaches were significant (P 0.05), as well as between the two anterolateral tibial tunnel approaches (T4–T5). The patient's anthropomorphic characteristics of sex, age, and height were not associated with the PSAs. Conclusions The PSA varied with the anteromedial, tibial crest and anterolateral approaches for transtibial PCL reconstruction, and surgeons should limit the PCL drill guide by referring to the specific PSA for different surgical approaches.

Next‐generation sequencing (NGS) has developed rapidly in the last decade and is emerging as a promising diagnostic tool for periprosthetic joint infection (PJI). However, its diagnostic value for PJI is still uncertain. This systematic review aimed to explore the diagnostic value of NGS for PJI and verify its accuracy for culture‐negative PJI patients. We conducted this systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines. Medline, Embase, and Cochrane Library were searched to identify diagnostic technique studies evaluating the accuracy of NGS in the diagnosis of PJI. The diagnostic sensitivity, specificity, and positive and negative predictive values were estimated for each article. The detection rate of NGS for culture‐negative PJI patients or PJI patients with antibiotic administration history was also calculated. Of the 87 identified citations, nine studies met the inclusion criteria. The diagnostic sensitivities and specificities of NGS ranged from 63% to 96% and 73% to 100%, respectively. The positive and negative predictive values ranged from 71% to 100% and 74% to 95%, respectively. The detection rate of NGS for culture‐negative PJI patients in six studies was higher than 50% (range from 82% to 100%), while in three studies it was lower than 50% (range from 9% to 31%). Also, the detection rate of NGS for PJIs with antibiotic administration history ranged from 74.05% to 92.31%. In conclusion, this systematic review suggests that NGS may have the potential to be a new tool for the diagnosis of PJI and should be considered to be added to the portfolio of diagnostic procedures. Furthermore, NGS showed a favorable diagnostic accuracy for culture‐negative PJI patients or PJI patients with antibiotic administration history. However, due to the small sample sizes of studies and substantial heterogeneity among the included studies, more research is needed to confirm or disprove these findings.

Background The anatomical positioning of the graft during anterior cruciate ligament reconstruction (ACLR) is of great significance for restoring normal knee kinematics and preventing early joint degeneration. Therefore, the adjustment of the mispositioned guide pin becomes extremely important. Our research aims to test the time-zero biomechanical properties in adjusting inaccurate guide pins to the center of the tibial footprint in anatomical anterior cruciate ligament single-bundle reconstruction. Methods Porcine tibias and bovine extensor tendons were used to simulate a transtibial ACL reconstruction in vitro. Load-to failure testing was carried out in 4 groups: control group ( n = 45): the guide pin was drilled at the center of the ACL footprint; group I, group II and group III ( n = 45, respectively): the guide pin was respectively drilled 1 mm, 2 mm and 3 mm away from the center of the ACL footprint. In the experimental groups, a small tunnel with a 4.5 mm reamer is made and the guide pin is shifted to the center of the footprint. All the reamed tibias were scanned by CT to measure the area of the tunnel in the footprint, and time-zero biomechanical properties were recorded. Results All graft-tibia complexes failed because the grafts slipped past the interference screws. Compare to control group, the ultimate load, yield load, and tunnel exit area in group III decreased significantly ( p < 0.05). Regarding to the ultimate load, yield load, tensile stiffness, twisting force and tunnel exit area, t-test showed no significant differences between control group and group I, group II respectively ( p > 0.05). Pearson test showed that tunnel exit area was negatively correlated with other characteristics ( p < 0.05). Conclusions Surgical adjustment of the guide pin to the center of the tibial footprint may have significant influence in time-zero biomechanical properties in anatomical anterior cruciate ligament single-bundle reconstruction when the adjusted tibial tunnel was significantly enlarged compare to the standard tibial tunnel.

Tendon-bone insertion (TBI) injuries are common, primarily involving the rotator cuff (RC) and anterior cruciate ligament (ACL). At present, repair surgery and reconstructive surgery are the main treatments, and the main factor determining the curative effect of surgery is postoperative tendon-bone healing, which requires the stable combination of the transplanted tendon and the bone tunnel to ensure the stability of the joint. Fibrocartilage and bone formation are the main physiological processes in the bone marrow tract. Therefore, therapeutic measures conducive to these processes are likely to be applied clinically to promote tendon-bone healing. In recent years, biomaterials and compounds, stem cells, cell factors, platelet-rich plasma, exosomes, physical therapy, and other technologies have been widely used in the study of promoting tendon-bone healing. This review provides a comprehensive summary of strategies used to promote tendon-bone healing and analyses relevant preclinical and clinical studies. The potential application value of these strategies in promoting tendon-bone healing was also discussed.

Mangiferin is a xanthone glucoside extracted from multiple plants, which has been shown to inhibit bone resorption and alleviate osteoporosis. However, the effect of purified Mangiferin on osteoporosis and its specific mechanisms is unknown. This study aimed to explore whether Mangiferin can promote osteogenic differentiation and alleviate osteoporosis in ovariectomized (OVX) mice and explore the potential mechanisms. Different concentrations and durations of Mangiferin were applied to MC3T3-E1 cells. The optimal concentration and duration of Mangiferin were determined by evaluating the cell viability via cell count kit-8 (CCK-8). The gene and protein expressions of AXL, ERK5, and osteogenic differentiation markers, including BMP2, Collagen1, OPN, Osterix, and Runx2, were detected using western blotting, qRT-PCR, immunofluorescence, and flow cytometry. Mangiferin was administered to OVX mice, and the severity of osteoporosis was evaluated by H and E staining, immunohistochemistry (IHC), microscopic computed-tomography (micro-CT) scanning, western blotting, and immunofluorescence of bone tissue. We found that Mangiferin promoted osteogenic differentiation in a dose-dependent manner at concentrations less than 30 μM. The 30 μM Mangiferin significantly upregulated the expression of AXL, ERK5, and osteogenic differentiation, including the ALP activity, percentage of alizarin red, and the levels of osteogenic differentiation markers. However, these expression levels decreased when AXL was knocked down in MC3T3-E1 cells and it could not be rescued by Mangiferin. Mangiferin relieved osteoporosis in OVX mice without causing severe organ damage. This study concluded that Mangiferin promoted osteogenic differentiation of MC3T3-E1 cells and alleviated osteoporosis in OVX mice. The potential mechanism was via the AXL/ERK5 pathway.

Abstract Background Many studies have shown that lipids play important roles in bone metabolism. However, the association between high-density lipoprotein cholesterol (HDL-C) and bone mineral density (BMD) is unclear. Therefore, this study aimed to investigate the linear or nonlinear relation between HDL-C levels and BMD and addressed whether the HDL-C levels had the potential values for predicting the risk of osteoporosis or osteopenia. Methods Two researchers independently extracted all information from the National Health and Nutrition Examination Survey (NHANES) database. Participants over 20 years of age with available HDL-C and BMD data were enrolled in the final analysis. The linear relationship between HDL-C levels and BMD was assessed using multivariate linear regression models. Moreover, the nonlinear relationship was also characterized by fitted smoothing curves and generalized additive models. In addition, the odds ratio (OR) for osteopenia and osteoporosis was evaluated with multiple logistic regression models. Results The weighted multivariable linear regression models demonstrated that HDL-C levels displayed an inverse association with BMD, especially among females and subjects aged 30 to 39 or 50 to 59. Moreover, the nonlinear relationship characterized by smooth curve fittings and generalized additive models suggested that (i) HDL-C levels displayed an inverted U-shaped relationship with BMD among women 30 to 39 or over 60 years of age; (ii) HDL-C levels exhibited a U-shaped association with BMD among women 20 to 29 or 50 to 59 years of age. In addition, females with high HDL levels (62-139 mg/dL) had an increased risk of osteopenia or osteoporosis. Conclusion This study demonstrated that HDL-C levels exhibit an inverse correlation with BMD. Especially in females, clinicians need to be alert to patients with high HDL-C levels, which may indicate an increased risk of osteoporosis or osteopenia. For these patients, close monitoring of BMD and early intervention may be necessary.

BackgroundThis study aimed to investigate the association between the systemic immune-inflammation index (SII) and bone mineral density (BMD) and to determine the association between the SII and the risk of osteopenia/osteoporosis among postmenopausal women aged ≥50 years.MethodsPostmenopausal women aged ≥50 years from the National Health and Nutrition Examination Survey were included. BMD testing was performed using dual-energy X-ray absorptiometry. The SII was calculated based on lymphocyte (LC), neutrophil (NC), and platelet (PC) counts. Moreover, the associations of BMD with SII and other inflammatory markers, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), the product of platelet count and neutrophil count (PPN), PC, NC, and LC, were assessed using a multivariable weighted linear regression model. Additionally, the associations of low BMD/osteoporosis with SII and other inflammatory markers were assessed using multivariable weighted logistic regression.ResultsFinally, a total of 893 postmenopausal women with a weighted mean age of 60.90 ± 0.26 years were included finally. This study found that SII was negatively associated with total femur BMD and femoral neck BMD, and postmenopausal women in a higher SII quarter group showed low lumbar spine BMD than the lowest SII quarter group when SII was converted from a continuous variable to a categorical variable. Moreover, increased SII was associated with an increased risk of low BMD and osteoporosis. In addition, this study observed that other inflammatory markers, especially NLR and PPN, were negatively associated with BMD and positively associated with the risk of osteoporosis. Finally, the subgroup analysis showed that the associations between BMD and inflammatory markers were pronounced in postmenopausal women aged ≥65 years or those with normal BMI (

Abstract Background Interference screw is commonly used for graft fixation in anterior cruciate ligament (ACL) reconstruction. However, previous studies had reported that the insertion of interference screws significantly caused graft laceration. The purposes of this study were to (1) quantitatively evaluate the graft laceration from one single insertion of PEEK interference screws; and (2) determine whether different types of sutures reduced the graft laceration after one single insertion of interference screws in ACL reconstruction. Methods The in-vitro ACL reconstruction model was created using porcine tibias and bovine extensor digitorum tendons of bovine hind limbs. The ends of grafts were sutured using three different sutures, including the bioabsorbable, Ethibond and ultra-high molecular weight polyethylene (UHMWPE) sutures. Poly-ether-ether-ketone (PEEK) interference screws were used for tibial fixation. This study was divided into five groups (n = 10 in each group): the non-fixed group, the non-sutured group, the absorbable suture group, the Ethibond suture group and the UHMWPE suture group. Biomechanical tests were performed using the mode of pull-to-failure loading tests at 10 mm/min. Tensile stiffness (newtons per millimeter), energy absorbed to failure (in joules) and ultimate load (newtons) were recorded for analysis. Results All prepared tendons and bone specimens showed similar characteristics (length, weight, and pre-tension of the tendons, tibial bone mineral density) among all groups (P > 0.05). The biomechanical tests demonstrated that PEEK interference screws significantly caused the graft laceration (P 0.05). Conclusions Our biomechanical study suggested that the ultimate failure load of grafts was reduced of approximately 25 % after one single insertion of a PEEK interference screw in ACL reconstruction. Suturing the ends of the grafts using different sutures (absorbable, Ethibond and UHMWPE sutures) did not decrease the graft laceration caused by interference screws.

Abstract Background Fibrinogen (FIB) has been found to be a promising marker in diagnosing periprosthetic joint infection (PJI), however, the value of FIB in predicting reinfection of PJI is unknown. The purpose of this study was to evaluate the value of FIB in predicting reinfection after debridement, antibiotics, and implant retention (DAIR) for PJI. Methods We retrospectively analyzed the clinical data of patients who were diagnosed with PJI and underwent DAIR from 2013 to 2019. The levels of the FIB, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were measured before DAIR. After DAIR, patients were followed and reinfections were identified. For both acute and chronic PJI, the predictive value of FIB was evaluated by calculating the sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic curve (ROC), and was compared with traditional inflammatory markers including ESR and CRP. Results The expression of FIB differed between patients reinfected and those not reinfected in both acute and chronic PJI (p

Objective. Neuropathic pain (NP) is a type of intractable chronic pain with complicated etiology. The exact molecular mechanism underlying NP remains unclear. In this study, we searched for molecular biomarkers of NP. Methods. Differentially expressed genes (DEGs) were predicted by analyzing three NP-related microarray datasets in Gene Expression Omnibus with robust rank aggregation. A weighted gene coexpression network analysis was conducted to construct a network of differentially expressed genes, followed by the evaluation of correlations between gene sets and the determination of hub genes. The candidate genes from the key module were identified using a gene set enrichment analysis. Results. In total, 353 upregulated and 383 downregulated genes were obtained, among which five hub genes were determined to be related to pain phenotypes. Reverse transcription-quantitative polymerase chain reaction was performed to verify the expression of these hub genes in the dorsal root ganglia of rats with spared nerve injury, which revealed the decreased expression of EMC4. Hence, EMC4 was defined as a biomarker for NP development. Conclusions. The results of this study form a basis for further research into the mechanism of NP development and are expected to aid in the development of novel therapeutic strategies.

Background: Previous studies had revealed that Body Mass Index (BMI) positively affected Bone Mineral Density (BMD). However, an excessively high BMI was detrimental to health, especially for the elderly. Moreover, it was elusive how much BMI was most beneficial for BMD in older adults to maintain.Objective: To investigate whether there was a BMI saturation effect value that existed to maintain optimal BMD.Methods: A cross-sectional study was conducted using the datasets of the National Health and Nutrition Examination Survey (NHANES) 2005–2006, 2007–2008, 2009–2010, 2013–2014, and 2017–2018. After adjusting for covariates, an analysis of the association between BMI and BMD in different femoral regions (Total femur, Femoral neck, Trochanter, Intertrochanter, and Ward's triangle) and lumbar spine regions (Total spine, L1, L2, L3, and L4) in the whole population was performed using the multivariate linear regression models, smoothing curve fitting, and saturation effects analysis models. Then, subgroup analyses were performed according to gender, age, and race.Results: A total of 10,910 participants (5,654 males and 5,256 females) over 50 years were enrolled in this population-based study. Multivariate linear regression analyses in the population older than 50 years showed that BMI was positively associated with femoral BMD and lumbar spine BMD (P < 0.001, respectively). Smoothing curve fitting showed that the relationship between BMI and BMD was not simply linear and that a saturation value existed. The saturation effect analysis showed that the BMI saturation value was 26.13 (kg/m2) in the total femur, 26.82 (kg/m2) in the total spine, and showed site-specificity in L1 (31.90 kg/m2) and L2 (30.89 kg/m2). The saturation values were consistent with the whole participants in males, while there was high variability in the females. BMI saturation values remained present in subgroup analyses by age and race, showing specificity in some age (60–70 years old) groups and in some races.Conclusions: Our study showed a saturation value association between BMI and BMD for people over 50 years old. Keeping the BMI in the slightly overweight value (around 26 kg/m2) might reduce other adverse effects while obtaining optimal BMD.

Background: Arthritis with severe varus deformity remains a challenge in total knee arthroplasty (TKA). Until recently, surgeons aimed at a neutral lower limb alignment when performing a TKA. However, the impact of TKA on the ankle joint has been ignored. Therefore, we conducted a systematic review to assess the clinical and radiological changes in the ankle joint after TKA on knees with severe varus deformity.Methods: A systematic search was conducted in four English (PubMed, Embase, Cochrane Library, and Web of Science) and four Chinese (CBM, VIP, CNKI, and Wan Fang Database) databases. Screening of literature and extraction of data were independently performed by two researchers. The modified methodological index for non-randomized studies (MINORS) was used to assess the quality.Results: A total of eight studies were eligible, namely, four prospective and four retrospective studies. TKA resulted in a negative clinical effect in the ankle joint in patients with ankle osteoarthritis. Seven studies reported changes in the mechanical tibiofemoral angle, and four studies reported radiological changes in the hindfoot. The mean score of the MINORS was 9.8 out of eight (9–11).Conclusion: As a result of the correction of the knee osteoarthritis with severe varus deformity following mechanically aligned TKA, the radiological malalignment of the ankle joint was improved. However, some patients experience increased ankle pain after undergoing TKA, especially, if there was a residual knee varus deformity, a stiff hindfoot with varus deformity, or ankle arthritis.

Purpose: To report of efficacy repair treatment for meniscus posterior root tears repair. Methods: We systematically searched databases including PubMed, Embase, and Cochrane Library for relevant articles. Coleman Methodology Score was used for a quality assessment of the included studies. A meta-analysis was performed to analyze for efficacy of MMPRTs repair. Results: Twenty-two studies, 14 level III and 8 level IV, were included in this systematic review, with a total of 926 cases. Studies comparing repair with either meniscectomy or conservative treatment found greater improvement and slower progression of Kellgrene–Lawrence grade with meniscal repair. Decreased meniscus extrusion is beneficial to the prognosis of patients undergoing MMPRTs repair. As treatment efficacy, the Lysholm score increased 28.87 (P < 0.001), IKDC score increased 31.73. The overall pooled event rates of progression of K-L grade is 0.200. Difference of Lysholm score and IKDC score between repair and meniscectomy were 8.72 and 9.67. Conclusions: The clinical subjective score after MMPRT repair was significantly improved compared with the preoperative status. Considering the progression of joint K-L grade, it can prevent the progression of arthrosis to some extent, but not completely. Decreased meniscus extrusion is beneficial to the prognosis of patients undergoing MMPRTs repair. Based on these results, MMPRTs repair cloud result favorable outcomes.

Abstract Background “Killer turn” effect is a critical explanation for the recurrent posterior laxity following transtibial posterior cruciate ligament (PCL) reconstruction, which affected by the angle of the tibial tunnel. Meanwhile, excessive tunnel angle would have an adverse impact on the healing of tendon to bone. The purpose was to evaluate the theoretical optimal angle of the tibial tunnel in transtibial anatomic PCL reconstruction. Methods The measurements were performed on CT sagittal plane, including the thickness of cancellous bone (L1), the theoretical optimal angle of the tibial tunnel (TOA, which was measured between tibial plateau and the extension cord connecting the center of PCL insertion site with a point 5 mm superior from marrow cavity vertex), L2 - the distance from anterior tunnel aperture to anterior end of tibial plateau, L3 - the distance from anterior tunnel aperture to tibial tuberosity (lowest edge of patellar ligament attachment). Results The value of TOA and L3 were 35.4 ± 7.9 ° and 26.8 ± 11.4 mm, respectively. L1 and L2 were higher in males than females (L1, P = 0.002; L2, P = 0.046). Regarding age, L1, TOA, L2 and L3 were higher in the 46–60 years group than 31–45 years group (P = 0.02, P = 0.001, P = 0.038, P = 0.032, respectively). With regard to height, L1 was lower in group I - 1.75 m (I v II, P = 0.015, I v III, P = 0.026). L2 was also lower in group I than group II and group III (I v II, P = 0.026, I v III, P = 0.006). TOA and L3 showed no significant differences among sex and height groups (P > 0.05). Conclusions TOA (35.4 ° ± 7.9 °) and L3 (26.8 ± 11.4 mm) could be used as a reference for ideal tibial tunnel placement in transtibial anatomic PCL reconstruction, so as to prevent recurrent PCL laxity and ensure good graft healing. However, further clinical validation is needed.