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Introduction: Pre-eclampsia complicates 4.6% of pregnancies and is linked to impaired placentation; likely due to dysregulated vasculogenesis/angiogenesis. Proteoglycans, such as biglycan, are located on the endothelial surface of fetal capillaries. Biglycan is reduced in the placenta of pregnancies complicated by fetal growth restriction and pre-eclampsia. Importantly, biglycan stimulates angiogenesis in numerous tissues. Therefore, this study investigated whether biglycan knockdown in mice results in a pre-eclamptic phenotype.Methods: Wild-type (WT) and Bgn-/- mice underwent cardiorenal measurements prior to and during pregnancy. One cohort of mice underwent post-mortem on gestational day 18 (E18) and another cohort underwent post-mortem on postnatal day 1 (PN1), with maternal and offspring tissues of relevance collected.Results: Bgn-/- dams had increased heart rate (+9%, p < 0.037) and reduced systolic (-11%, p < 0.001), diastolic (-15%, p < 0.001), and mean arterial (-12%, p < 0.001) pressures at all ages investigated compared to WT. Additionally, Bgn-/- dams had reduced urine flow rate (-64%, p < 0.001) as well as reduced urinary excretions (-49%, p < 0.004) during late gestation compared to WT. Bgn-/- pups had higher body weight (+8%, p = 0.004; E18 only) and a higher liver-to-brain weight ratio (+43%, p < 0.001). Placental weight was unaltered with only minor changes in vasculogenic and angiogenic gene abundances detected, which did not correlate to changes in protein expression.Discussion: This study demonstrated that total knockdown of biglycan is not associated with features of pre-eclampsia. [ABSTRACT FROM AUTHOR]

Objective: To delineate the activities of decorin and biglycan in the progression of post-traumatic osteoarthritis (PTOA).Design: Three-month-old inducible biglycan (BgniKO) and decorin/biglycan compound (Dcn/BgniKO) knockout mice were subjected to the destabilization of the medial meniscus (DMM) surgery to induce PTOA. The OA phenotype was evaluated by assessing joint structure and sulfated glycosaminoglycan (sGAG) staining via histology, surface collagen fibril nanostructure and calcium content via scanning electron microscopy, tissue modulus via atomic force microscopy-nanoindentation, as well as subchondral bone structure and meniscus ossification via micro-computed tomography. Outcomes were compared with previous findings in the inducible decorin (DcniKO) knockout mice.Results: In the DMM model, BgniKO mice developed similar degree of OA as the control (0.44 [-0.18 1.05] difference in modified Mankin score), different from the more severe OA phenotype observed in DcniKO mice (1.38 [0.91 1.85] difference). Dcn/BgniKO mice exhibited similar histological OA phenotype as DcniKO mice (1.51 [0.97 2.04] difference vs control), including aggravated loss of sGAGs, salient surface fibrillation and formation of osteophyte. Meanwhile, Dcn/BgniKO mice showed further cartilage thinning than DcniKO mice, resulting in the exposure of underlying calcified tissues and aberrantly high surface modulus. BgniKO and Dcn/BgniKO mice developed altered subchondral trabecular bone structure in both Sham and DMM groups, while DcniKO and control mice did not.Conclusion: In PTOA, decorin plays a more crucial role than biglycan in regulating cartilage degeneration, while biglycan is more important in regulating subchondral bone structure. The two have distinct activities and modest synergy in the pathogenesis of PTOA. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the functional effect of implicated variants within BGN and COL5A1 on gene expression of components of the extracellular matrix (ECM) in a TGF-β-stimulated risk model for musculoskeletal soft tissue injuries.Design: Experimental research, laboratory study.Methods: Skin biopsies were obtained from nine healthy participants with either a combined increased or reduced risk profile for COL5A1 rs12722 C>T and BGN rs1126499 C>T - rs1042103 G>A, and primary fibroblast cell lines were established. Total RNA was extracted at baseline (10% FBS), after serum starvation (1% FBS) and TGF-β1 treatment (1% FBS, 10ng/mL TGF-1β). Relative mRNA levels of BGN, COL5A1, DCN and VEGFA was quantified using Taqman® array pre-spotted plate assays (Applied Biosystems, Foster city, CA, USA).Results: At baseline, the reduced risk group had 2.5, 1.9 and 2 fold increases (p<0.001) in relative BGN, COL5A1 and VEGFA mRNA levels respectively. In the serum starved experiments, except for a significant 1.5 fold (p=0.017) increase in relative DCN mRNA expression in the reduced risk group, similar observations were noted for the other three genes. After TGF-1β treatment, the reduced risk group had 1.3 (p=0.011) and 1.4 fold (p=0.001) increases in the relative COL5A1 and VEGFA mRNA levels, respectively.Conclusions: Altered mRNA levels associated with genetic risk profiles for musculoskeletal soft injury risk at baseline (BGN, COL5A1 and VEGFA), with serum starvation (DCN) and after TGF-β1 treatment (COL5A1 and VEGFA) provide additional functional evidence to support the association of implicated genetic loci with several musculoskeletal soft tissue injuries. Implication of altered gene expression profiles underpinning these genetic risk associated loci potentially highlight key therapeutic targets for management of these injuries. [ABSTRACT FROM AUTHOR]

Proteoglycans are considered integral structural components of tendon and ligament and have been implicated in the resistance of compressive forces, collagen fibrillogenesis, matrix remodelling and cell signalling. Several sequence variants within genes encoding proteoglycans were recently implicated in modulating anterior cruciate ligament ruptures (ACLR). This study aimed to test the previously implicated variants in proteoglycan and vascular epithelial growth factor encoding genes with risk of ACLR in a population from Poland. A case control genetic association study was conducted using DNA samples from 143 healthy participants without a history of ACL injuries (99 male and 44 females) (CON group) and 229 surgically diagnosed ACLR participants (158 males and 71 females). All samples were genotyped for the ACAN: rs1516797, BGN: rs1042103, rs1126499, DCN: rs516115 and VEGFA: rs699947 variants. Main findings included the (i) ACANrs1516797 G/T genotype which was underrepresented in the CON group (CON: 36%, n = 52, ACLR: 49%, n = 112, p=0.017, OR=1.68, 95% CI 1.09 to 2.57) when all participants were investigated and (ii) the BGN rs1042103 A allele was significantly under-represented in the male CON group compared to the male ACLR group (CON: 39%, n = 78, ACLR: 49%, n = 156, p=0.029, OR=1.5, 95% CI 1.05 to 2.15). Furthermore, BGNinferred haplotypes were highlighted with altered ACLR susceptibility. Although the study implicated the ACAN and BGN genes (combination of genotype, allele and haplotype) in modulating ACLR susceptibility, several differences were noted with previous published findings. [ABSTRACT FROM AUTHOR]

Esophageal cancer has been reported in various countries, including Saudi Arabia, India and United States. Many biomarkers have been used to detect cancers at an early stage to improve the survival rate of esophageal cancer. The present study investigated the biomarkers, biglycan, myeloperoxidase, cytokine (TNF-α, IFN-γ, IL-10 and IL-12) and carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and carbohydrate antigen L1 cell adhesion molecule from the tumour and non-tumour samples. The increased amount of circulatory biglycan level was detected using the ELISA method in tumour cases compared to control samples (p < 0.001). The expression of biglycan was high in certain tumour cases and was statistically significant (p < 0.01). The variation of myeloperoxidase markers in control and experimental subjects were statistically significant (p < 0.01). Among cancer patients, elevated levels of carcinoembryonic antigen (28.3 ± 1.2 ng/ml and 30.3 ± 1.1 ng/ml), squamous cell carcinoma antigen (5.3 ± 1.1 ng/ml and 4.9 ± 0.5) and carbohydrate antigen 19–9 (18.3 ± 1.1 ng/ml and 15.1 ± 2.6 ng/ml) were detected in male and female cases (p < 0.001). In the normal tissues, the expression of L1 cell adhesion molecule was high and was expressed in low amount in tumour tissues in both male and female individuals (<0.001). These biomarkers are useful for the early diagnosis of esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: The extracellular matrix (ECM) plays an important role in left ventricular remodeling and progression of heart failure (HF). Biglycan and mimecan are ECM proteins that are abundantly expressed in cardiac tissue but have not been evaluated as prognostic markers in HF. We investigated their interaction with statin treatment and association with adverse outcome in chronic HF. Methods and Results: The association between serum levels of biglycan and mimecan and the primary end point (cardiovascular [CV] death, nonfatal myocardial infarction, nonfatal stroke), all-cause mortality, CV death, the composite of all-cause mortality/hospitalization for worsening of HF, and the coronary end point was evaluated in 1,390 patients >60 years of age with ischemic systolic HF in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) population, randomly assigned to 10 mg rosuvastatin or placebo. Serum biglycan and mimecan added no prognostic information beyond conventional risk factors, including N-terminal pro--B-type natriuretic peptide. However, statin treatment improved all outcomes except CV death in patients with low biglycan levels (ie, lower tertile), even after full multivariable adjustment. Conclusions: Although circulating levels of mimecan and biglycan were of limited predictive value in patients with chronic HF, circulating biglycan could be a useful marker for targeting statin therapy in patients with HF. [ABSTRACT FROM AUTHOR]

The article presents a study on the expression of the small leucine-rich proteoglycans (SLRPs) fibromodulin, biglycan and decorin in the retinas of imprinting control region (ICR) mice. The researchers bought ICR mice from CLEA Japan Inc. in Tokyo, which were maintained with a 12:12 hour light-dark cycle with free water and food access throughout the study. They also used hematoxylin and eosin (HE) to stain the retinal sections at a distance of 1 millimeter from the optic disc. They found that fibromodulin and decorin might contribute to the damage and repair process of the retina but biglycan would not.

Abstract: Objective: The proteoglycan decorin stabilizes collagen whereas biglycan and hyaluronan disrupt well-organized collagen. The aim was to compare hyaluronan and proteoglycans in human fetal membranes obtained before and after spontaneous labour at term. Study design: Prelabour samples of fetal membranes (N =9) were obtained from elective caesarean sections and regionally sampled from over the cervix (cervical membranes) and mid-zone samples between this area and the placental edge. Postlabour samples (N =11) were obtained from spontaneous vaginal delivery and also regionally sampled. Amnion and chorio-decidua were analysed separately. The proteoglycans decorin and biglycan were analysed using alcian blue precipitation, SDS polyacrylamide gel electrophoresis and immunostaining. Hyaluronan was analysed using a radioimmunoassay and by histochemistry. Collagen was measured by estimating hydroxyproline content. Results: In prelabour membranes the biglycan concentration (μg/mg wtw) in the cervical amnion was 40% lower than in the mid-zone amnion (P <0.05). After delivery the cervical amnion showed a twofold increase in biglycan (P <0.05), a 30% decrease in collagen (P <0.05), and a 50% decrease in decorin concentration (P <0.05). In mid-zone samples after delivery the concentrations of hyaluronan showed an increase form 1.0 to 4.9μg/mg wtw (P <0.05). Histology demonstrated a gelatinous substance, which separated amnion and chorio-decidua, in particular at the cervical site. This gelatinous substance contained hyaluronan at a concentration of 3.0μg/mg wtw. Conclusion: It is well established that prelabour fetal membranes are considerably stronger than postlabour fetal membranes. Two features may explain this; a weakening of the amnion combined with a separation of amnion and chorio-decidua. The biomechanical changes are consistent with the decrease in collagen and decorin, and the increase in hyaluronan and biglycan demonstrated in this study. The separation of the membranes is caused by the formation of a gelatinous substance, rich in hyaluronan. The results indicate that the biomechanical changes are not merely secondary to the stress of labour but that an active maturation process is involved. [Copyright &y& Elsevier]

Abstract: Impaired glucose metabolism with diabetes may alter the expressions of proteoglycans (PGs), which may impair the biological functions of placenta. In this study, we investigated the expression of PGs and their conjugated glycosaminoglycan (GAG) composition in the placentas of mothers with gestational diabetes mellitus (GDM) and trophoblasts cultured in a high-glucose condition. The PGs by guanidine/HCl extraction and DEAE Sepharose fractionation followed by GAG degradation enzyme digestion analyses showed that the expression of chondroitin sulfate and/or dermatan sulfate (CS/DS) PGs was increased whereas the heparan sulfate (HS) PG was decreased in GDM placentas compared to controls. Western blot analyses demonstrated that the increased CS/DS PGs in GDM placentas were predominantly the small leucine-rich proteoglycans (SLRPs), decorin and biglycan. Increased mRNA expression level was consistently shown by quantitative real-time PCR. Immunohistochemistry indicated intensive staining of decorin and biglycan in the diabetic placenta with different localizations. Additionally, the basement membrane HSPG, perlecan was found to contain both CS/DS and HS in GDM placentas and plain HS in controls. Similar findings of PG alterations induced by hyperglycemia were observed in cultured trophoblast in a high-glucose condition. This study demonstrated that hyperglycemia induced not only the gene expressions of PGs but also alterations in the carried GAG type and composition. [Copyright &y& Elsevier]

Objective: To investigate whether the absence of biglycan and fibromodulin, two proteoglycans expressed in cartilage, bone and tendon, resulted in accelerated osteoarthritis in the temporomandibular joint (TMJ).Methods: Histological sections of TMJ from 3-, 6-, 9- and 18-month-old wild-type (WT) and biglycan/fibromodulin double-deficient (DKO) mice were compared. Immuno-stainings for biglycan, fibromodulin and proliferating cell nuclear antigen (PCNA) were performed.Results: Biglycan and fibromodulin were highly expressed in the disc and articular cartilage of the TMJ. At 3 months of age, both WT and DKO presented early signs of cartilage degeneration visible as small acellular areas under the articular surfaces and superficial waving. From 6 months of age, DKOs developed accelerated osteoarthritis compared to WT. At 6 months, small vertical clefts in the condylar cartilage and partial disruption of the disk were visible in the DKO. In addition, chondrocytes had lost their regular columnar organization to form clusters. At 9 months, these differences were even more pronounced. At 18 months, extended cartilage erosion was visible in DKOs when by comparison the thickness of the articular cartilage in WT controls was basically intact. PCNA staining was stronger in 3-month-old WT TMJ fibrocartilage than in 3-month-old DKO TMJ fibrocartilage suggesting that chondrocyte proliferation might be impaired in DKOs.Conclusion: The biglycan/fibromodulin double knock-out mouse constitutes a useful animal model to decipher the pathobiology of osteoarthritis in the TMJ. [ABSTRACT FROM AUTHOR]

Biglycan is a member of the small leucine repeat proteoglycan family (SLRP). The biglycan gene is located on the X chromosome. Based on the amino add sequence, the protein core of biglycan can be divided into six distinct domains: (1) a signal sequence, (2) a propeptide region, (3) a N-terminal glycosaminoglycan attachment region, (4) a cysteine loop, followed by (5) a leucine- rich repeat region domain (that makes up over 66% of the core protein), and (6) a final cysteine loop. Biglycan has been found in almost every organ within our body, but it is not uniformly distributed within an organ. Biglycan has been shown to be expressed on the cell surface, pericellularly, and sometimes within the extracellular matrices of a range of specialized cell types within the organ. Its expression pattern has been shown to be altered by growth factors and certain pathologic conditions. The regulation of biglycan expression occurs by both transcriptional and nontranscriptional mechanisms. The currently proposed biglycan functions appear to be dependent on the particular microenvironment and on the organ in question. In this review, we will focus on gene and protein structure, localization, expression, regulation, and function. [ABSTRACT FROM AUTHOR]