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Aging-related osteoarthritis (OA) is the most common type of arthritis. Chondrocyte senescence has been linked with the pathogenesis of OA. Here, we examined the expression of GPR39 in chondrocytes and its modulatory effect on IL-1β-induced cellular senescence. We show that GPR39 is moderately expressed in human chondrocytes and its expression is repressed by the pro-inflammatory cytokine IL-1β. The GPR39 agonist TC-G 1008 mitigates IL-1β-induced chondrocyte senescence. Mechanistically, we show that TC-G 1008 mitigates IL-1β-induced cell cycle arrest at G1 phase by suppressing the expression of p53, p21, PAI-1, and K382 acetylation of p53. Moreover, we show that TC-G 1008 treatment restores IL-1β-induced inhibition of SIRT1 and the silencing of SIRT1 abolishes the function of TC-G 1008 on p53 acetylation and senescence, suggesting that the function of GPR39 signaling is mediated by SIRT1 in chondrocytes. Altogether, our findings implicate that the activation of GPR39 signaling ameliorates IL-1β-induced chondrocyte senescence and the GPR39 agonist TC-G 1008 could have the potential to modulate aging-associated OA. [ABSTRACT FROM AUTHOR]

Objectives: Rheumatoid arthritis (RA) is a common autoimmune disease. However, the positive diagnosis value of the current biomarkers is unsatisfactory. Here, we aimed to identify RA-associated susceptibility genes and explore their potential as novel biomarkers for the diagnosis of RA., Methods: Peripheral blood mononuclear cells (PBMCs) were collected from healthy controls and RA patients. RNA-seq and bioinformatics analyses were performed to identify the hub genes associated with RA. Then, the expression of hub genes was assessed in mRNA expression profiles from GEO datasets. Real time-quantitative PCR (RT-qPCR) was performed to further confirm the expression of the hub genes using the PBMCs that were collected from RA patients (n=47) and healthy controls (n=40). Finally, we evaluated the diagnostic potential of the candidate mRNAs., Results: RNA-seq analyses revealed 178 dysregulated genes measured by changes in mRNAs between the healthy controls and the RA patients. We identified 3 candidate mRNAs, including ASPM, DTL and RRM2, all of which were highly expressed in RA. RRM2 showed a significant higher expression in remissive RA compared with active RA. Significant correlations were observed between DTL and IL-8, TNF-α which were tested in serum by ELISA, between RRM2 and CDAI, DAS-28, tender and swollen joints, respectively. The expression level of RRM2 was significantly higher in RA patients with the Anti-CCP- than with the Anti-CCP+. The AUC (RA vs. OA) value of RRM2 was 0.941 (p<0.0001; sensitivity=0.867; specificity=0.904)., Conclusions: RRM2 showed high diagnosis efficiency for RA patients. Therefore, the findings provided a novel candidate biomarker for the diagnosis of RA.

Ossicle of the meniscus is an uncommon discovery often misdiagnosed as a loose body, which may lead to intermittent knee discomfort. We present a rare case of meniscal ossicle accompanied by the medial meniscus posterior root tear. A 46-year-old female experienced intermittent left knee pain and after coming to the hospital was diagnosed with a meniscal ossicle. The patient underwent arthroscopic ossicle resection followed by meniscal root repair. The patient had not experienced any complications post-operatively and remains asymptomatic 8 months after the surgery. The purpose of this article is to expand the knowledge of meniscal ossicle and provide a broaden review of its diagnosis and repair., Competing Interests: Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (© 2022 The Authors. Published by the British Institute of Radiology.)

Osteoarthritis is a major global health burden. Joint destruction resulting from excessive degradation of type II collagen and aggrecan in the articular extracellular matrix by metalloproteinases and aggrecanases, respectively, is a major pathological hallmark of osteoarthritis. However, the exact mechanisms remain poorly understood. Currently, there are few non-invasive therapies capable of slowing or halting the progression of the disease. In the present study, we investigated the involvement of the P2Y 11 purinergic protein and its receptor P2Y11R in TNF-α-mediated degradation of the extracellular matrix in SW1353 cell line chondrocytes using the novel P2Y11R antagonist NF157. To our knowledge, this is the first study to explore the effects of NF157 in OA. Our results indicate that P2Y11R may indeed play a role in TNF-α-induced degradation of extracellular matrix in OA as treatment with NF157 significantly reduced expression of metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5, and ameliorated degradation of type II collagen and aggrecan in SW1353 chondrocytes in a dose-dependent manner. Furthermore, we show that treatment with NF157 significantly reduced nuclear translocation of p65 and subsequent activation of nuclear factor κB (NF-κB)., Competing Interests: None.

Objectives: Osteoarthritis (OA), characterized by degradation of articular cartilage, is a leading cause of disability. As the only cell type present in cartilage, chondrocytes play curial roles in the progression of OA. In our study, we aimed to explore the roles of miR-23b in the lipopolysaccharide (LPS)-induced inflammatory injury., Materials and Methods: LPS-induced cell injury of ATDC5 cells was evaluated by the loss of cell viability, enhancement of cell apoptosis, alteration of apoptosis-associated proteins, and release of inflammatory cytokines. Then, miR-23b level after LPS treatment was assessed by qRT-PCR. Next, the effects of aberrantly expressed miR-23b on the LPS-induced inflammatory injury were explored. The possible target genes of miR-23b were virtually screened by informatics and verified by luciferase assay. Subsequently, whether miR-23b functioned through regulating the target gene was validated. The involved signaling pathways were investigated finally., Results: Cell viability was decreased but cell apoptosis, as well as release of inflammatory cytokines, was enhanced by LPS treatment. MiR-23b was down-regulated by LPS and its overexpression alleviated LPS-induced inflammatory injury. PDCD4, negatively regulated by miR-23b expression, was verified as a target gene of miR-23b. Following experiments showed miR-23b alleviated LPS-induced cell injury through down-regulating PDCD4 expression. Phosphorylated levels of key kinases in the NF-κB pathway, as well as expressions of key kinases in the Notch pathways, were increased by PDCD4 overexpression., Conclusion: MiR-23b was down-regulated after LPS treatment, and its overexpression ameliorated LPS-induced inflammatory injury in ATDC5 cells by targeting PDCD4, which could activate the NF-κB/Notch pathways.

To explore whether the over-expression of Sry-related HMG box (Sox9) in degenerative chondrocytes is able to improve cell regeneration and protects cells from inflammation induced apoptosis, we generated a Sox9 over-expressing vector delivery system in which the Sox9 gene was inserted into a lentiviral vector. After infecting mouse chondrocytes with the Sox9-encoding vector, we observed a high level of gene transduction efficiency and achieved a high level of Sox9 expression in the infected chondrocytes. To explore whether over-expression of Sox9 is able to induce cell regeneration and improve cell survival, we induced Sox9 over-expression by lentiviral vector infection 48 hours before IL-1β treatment. The cells were infected with the reporter gene GFP-encoded lentiviral vector as a negative control or left uninfected. 48-hours after IL-1β treatment, the chrondrocytes treated with IL-1β alone, underwent a degenerative process, with elevated expression of MMP-3, MMP-13, ADAMTS-5 and ALP, but the cell specific anabolic proteins collagen II and aggrecan were significantly suppressed. The cells infected with the GFP reporter vector had no increased regeneration after IL-1β treatment. The results indicated that Sox9 is an important chondrocyte transcription factor, promoting chondrocyte regeneration and cell survival, which were mediated through affecting multiple cell differentiation as well as anti-apoptotic signaling pathways.