Proteins In Osteoarthritis Research Articles

Cartilage Oligomeric Matrix Protein in Osteoarthritis and Obesity-Do New Considerations Emerge?

The diagnosis of osteoarthritis (OA) is based on radiological changes that are delayed, along with clinical symptoms. Early and very early diagnosis at the stage of molecular pathology may eventually offer an opportunity for early therapeutic intervention that may retard and prevent future damage. Cartilage oligomeric matrix protein (COMP) is a non-collagenous extracellular matrix protein that promotes the secretion and aggregation of collagen and contributes to the stability of the extracellular matrix. There are contradictory literature data and currently, the parameter is used only for scientific purposes and its significance is not well-determined. The serum level of COMP in patients with metabolic type OA of the knee has not been evaluated. The aim of the study was to analyze serum COMP levels in metabolic knee OA and controls with different BMI. Our results showed that the mean COMP values were significantly higher in the control group (1518.69 ± 232.76 ng/mL) compared to the knee OA patients (1294.58 ± 360.77 ng/mL) (p = 0.0012). This may be related to the smaller cartilage volume in OA patients. Additionally, COMP levels negatively correlated with disease duration (p = 0.04). The COMP level in knee OA with BMI below 30 kg/m2 (n = 61, 1304.50 ± 350.60 ng/mL) was higher compared to cases with BMI ≥ 30 kg/m2 (n = 76, 1286.63 ± 370.86 ng/mL), but the difference was not significant (p = 0.68). Whether this finding is related to specific features in the evolution of the metabolic type of knee OA remains to be determined. Interestingly, comparison of COMP levels in the controls with different BMI revealed significantly higher values in overweight and obese individuals (1618.36 ± 203.76 ng/mL in controls with BMI ≥ 25 kg/m2, n = 18, 1406.61 ± 216.41 ng/mL, n = 16; p = 0.0092). Whether this finding is associated with increased expression of COMP in the adipose tissue or with more intensive cartilage metabolism in relation to higher biomechanical overload in obese patients, considering the earlier development of metabolic type knee OA as an isolated finding, remains to be determined.

Unveiling the role of C-reactive protein in osteoarthritis: A biomarker of inflammation, severity, and degeneration

Unveiling the role of C-reactive protein in osteoarthritis: A biomarker of inflammation, severity, and degeneration

Isorhynchophylline alleviates cartilage degeneration in osteoarthritis by activating autophagy of chondrocytes

ContextOsteoarthritis is a common degenerative disease, the cause of it is still unknown, and the treatment mainly focuses on improving symptoms. Studies have found that Isorhynchophylline (Isorhy) has antioxidant, anti-inflammatory, antiproliferative and neuroprotective effects.ObjectiveThis study investigates the role and mechanism of Isorhy in OA.MethodsThe destabilized medial meniscus model was used to mimic OA. Fifteen male Sprague Dawley rats were partitioned into three portions: Normal group, OA group (surgery; normal saline treatment) and OA + Isorhy group (surgery; 50 μM Isorhy treatment) were performed on the first day of every week from the 5th to the 8th week after surgery. After 4 weeks of drug treatment, the rats have been processed without debridement of the knee specimens and fixed using 4% paraformaldehyde for two days. The morphological analysis was performed by H&E, Safranin O-Fast green staining and micro-CT analysis. The specimens were researched employing Micro-CT. In the part of the aggregate methods that were evaluated by qRT-PCR and western blot of the following proteins LC3II/LC3I, Beclin-1, ATG5, ATG7, MMP3 andMMP13. Akt/PI3K signaling related proteins (p-AKT, AKT, p-PI3K, PI3K, p-mTOR, mTOR) were detected by Western blot. BECLIN1 and MMP3 were detected by Immunofluorescence assay.ResultsIn this present research, it was proved that autophagy-related and cartilage matrix-related proteins in osteoarthritis could be regulated by Isorhynchophylline treatment. The transcriptome sequencing results suggested the regulation was closely associated with PI3K/AKT/mTOR pathway, thereby alleviating osteoarticular inflammation. In-depth study showed that Isorhy could also affect OA in rat OA models, that was indicated by H&E, Safranin O-Fast green staining, and also micro-CT analysis.ConclusionOur findings indicated that Isorhy could be regarded as a prospective candidate for OA treatment.

Establishment Of Regulatory Networks Of Cartilage Specific Differentially Expressed Proteins In Osteoarthritis

Establishment Of Regulatory Networks Of Cartilage Specific Differentially Expressed Proteins In Osteoarthritis

RNA binding proteins in osteoarthritis.

Osteoarthritis (OA) is a common chronic degenerative joint disease worldwide. The pathological features of OA are the erosion of articular cartilage, subchondral bone sclerosis, synovitis, and metabolic disorder. Its progression is characterized by aberrant expression of genes involved in inflammation, proliferation, and metabolism of chondrocytes. Effective therapeutic strategies are limited, as mechanisms underlying OA pathophysiology remain unclear. Significant research efforts are ongoing to elucidate the complex molecular mechanisms underlying OA focused on gene transcription. However, posttranscriptional alterations also play significant function in inflammation and metabolic changes related diseases. RNA binding proteins (RBPs) have been recognized as important regulators in posttranscriptional regulation. RBPs regulate RNA subcellular localization, stability, and translational efficiency by binding to their target mRNAs, thereby controlling their protein expression. However, their role in OA is less clear. Identifying RBPs in OA is of great importance to better understand OA pathophysiology and to figure out potential targets for OA treatment. Hence, in this manuscript, we summarize the recent knowledge on the role of dysregulated RBPs in OA and hope it will provide new insight for OA study and targeted treatment.

A molecular map of long non-coding RNA expression, isoform switching and alternative splicing in osteoarthritis.

Osteoarthritis is a prevalent joint disease and a major cause of disability worldwide with no curative therapy. Development of disease-modifying therapies requires a better understanding of the molecular mechanisms underpinning disease. A hallmark of osteoarthritis is cartilage degradation. To define molecular events characterizing osteoarthritis at the whole transcriptome level, we performed deep RNA sequencing in paired samples of low- and high-osteoarthritis grade knee cartilage derived from 124 patients undergoing total joint replacement. We detected differential expression between low- and high-osteoarthritis grade articular cartilage for 365 genes and identified a 38-gene signature in osteoarthritis cartilage by replicating our findings in an independent dataset. We also found differential expression for 25 novel long non-coding RNA genes (lncRNAs) and identified potential lncRNA interactions with RNA-binding proteins in osteoarthritis. We assessed alterations in the relative usage of individual gene transcripts and identified differential transcript usage for 82 genes, including ABI3BP, coding for an extracellular matrix protein, AKT1S1, a negative regulator of the mTOR pathway and TPRM4, coding for a transient receptor potential channel. We further assessed genome-wide differential splicing, for the first time in osteoarthritis, and detected differential splicing for 209 genes, which were enriched for extracellular matrix, proteoglycans and integrin surface interactions terms. In the largest study of its kind in osteoarthritis, we find that isoform and splicing changes, in addition to extensive differences in both coding and non-coding sequence expression, are associated with disease and demonstrate a novel layer of genomic complexity to osteoarthritis pathogenesis.

A novel regulatory role of trappc9 and L-plastin in osteoarthritis

A novel regulatory role of trappc9 and L-plastin in osteoarthritis

Proteomic Analysis of Synovial Fibroblasts and Articular Chondrocytes Co-Cultures Reveals Valuable VIP-Modulated Inflammatory and Degradative Proteins in Osteoarthritis.

Osteoarthritis (OA) is the most common musculoskeletal disorder causing a great disability and a reduction in the quality of life. In OA, articular chondrocytes (AC) and synovial fibroblasts (SF) release innate-derived immune mediators that initiate and perpetuate inflammation, inducing cartilage extracellular matrix (ECM) degradation. Given the lack of therapies for the treatment of OA, in this study, we explore biomarkers that enable the development of new therapeutical approaches. We analyze the set of secreted proteins in AC and SF co-cultures by stable isotope labeling with amino acids (SILAC). We describe, for the first time, 115 proteins detected in SF-AC co-cultures stimulated by fibronectin fragments (Fn-fs). We also study the role of the vasoactive intestinal peptide (VIP) in this secretome, providing new proteins involved in the main events of OA, confirmed by ELISA and multiplex analyses. VIP decreases proteins involved in the inflammatory process (CHI3L1, PTX3), complement activation (C1r, C3), and cartilage ECM degradation (DCN, CTSB and MMP2), key events in the initiation and progression of OA. Our results support the anti-inflammatory and anti-catabolic properties of VIP in rheumatic diseases and provide potential new targets for OA treatment.

Auto-antibodies to post-translationally modified proteins in osteoarthritis

Autoantibodies (AutoAbs) have been observed in osteoarthritis (OA) with broad antigenicity, although their prevalence and role remain unclear. Post-translational modification (PTMs) of proteins (oxidation, carbamylation, citrullination) is associated with synovitis and can lead to AutoAb development. Given the prevalence of synovitis, we explored whether AutoAbs to PTM-antigens are common in OA compared with rheumatoid arthritis (RA). Serum (n=895) was obtained from healthy controls, OA and RA patients; and arthritic synovial fluid (SF, n=290). ELISAs were used to quantify anti-citrullinated peptide (ACPA), anti-carbamylated protein (anti-CarP), anti-oxidized collagen (anti-ROS-CI/CII) antibodies. In sera, positivity for PTM-antigens AutoAbs was observed at a lower frequency in OA with 64.1% (95%CI: 57.2-70.1%) more ACPA+ and 29.8% (21.0-37.3%) more anti-CarP+patients in RA (both P<0.0001). Levels of ACPA, anti-CarP were also lower in OA (P<0.0001). Anti-ROS-CII positivity was lower in OA compared to RA (16.6%, 4.8-28.6%) less frequent, P=0.033) but not anti-native-CII. There was no impact of age/gender on AutoAbs associations with diseases either looking at positivity or levels. In SF, OA patients were often ACPA+ (45.9%) although less frequently than in RA (P=0.004). Anti-CarP were rarely observed (<5% all samples). All collagen AutoAbs were more frequent in RA compared to OA (all P<0.010) but only levels of anti-CII and anti-ROS-CII were significantly higher in they RA (P<0.050). Although the frequency of AutoAbs for PTM proteins were lower in OA sera compared to RA, a higher proportion of OA SF were positive. The relative retention of AutoAbs in the OA joint requires further investigation.

The role of thrombospondin-4 and the cartilage oligomeric matrix protein in osteoarthritis

Purpose: The hallmark of osteoarthritis (OA) is the continuous degradation of the cartilage extracellular matrix (ECM). Cartilage oligomeric matrix protein (COMP or thrombospondin-5) is ubiquitously expressed in the ECM of healthy cartilage, degraded in early OA, and re-expressed at a late stage of disease. The role of COMP is besides its cross-linking and stabilizing effect on the ECM still elusive. We hypothesized that in OA another ECM protein might compensate for the loss of COMP. Thrombospondin-4 (TSP-4), another member of the thrombospondin family and structurally similar to COMP, is known to be upregulated in injured tissues and associated with matrix remodeling and angiogenesis, could be such a candidate.

Differential expression of transient receptor potential vanilloid receptor 4 protein in osteoarthritis and normal cartilages

To investigate the differential expression of transient receptor potential vanilloid receptor 4 (TRPV4) protein in the osteoarthritis (OA) and normal cartilages, and explore the role of TRPV4 in the prevention and treatment of OA. The cartilage tissues from the patients of knee OA (OA group) and femoral neck fracture (control group) were taken. In OA group, there were 6 males and 9 females; the age ranged from 55 to 78 years (mean, 69 years); the Kellgren-Lawrence (K-L) score was 3.0±0.8. In control group, there were 5 males and 10 females; the age ranged from 57 to 91 years (mean, 71 years). There was no significant difference in gender and age between the two groups ( P>0.05). Western blot, real-time fluorescence quantitative PCR, Masson staining, and immunohistochemical staining were used to detect the difference in protein and mRNA expressions of TRPV4 between the OA and normal cartilages. Then the relationship between the K-L score of OA and the rate of TRPV4-positive cells was analyzed. The relative expression of TRPV4 protein and mRNA in OA group were 0.454±0.199 and 2.951±1.200, which were higher than those in control group (0.165±0.074, 1.437±0.682). The difference in relative expression of TRPV4 protein was significant ( t=2.718, P=0.026). Histology observation showed that the chondrocytes arranged disorderly in OA group, the structure of extracellular matrix was abnormal, and the cartilage defect reached the deep layer. There were more TRPV4-positive cells in the degenerated tissue, and the rate of TRPV4-positive cells was 37.353%±13.496%. The chondrocytes were arranged well in control group, and the rate of TRPV4-positive cells was only 9.642%±3.284%. There was a significant difference between the two groups ( t=7.491, P=0.000). The rate of TRPV4-positive cells in OA group was positively correlated with the OA K-L score ( r=0.775, P=0.001). The TRPV4 expression increased in OA cartilages that may contribute to the development of OA.

Genome-wide association and functional studies identify a role for matrix Gla protein in osteoarthritis of the hand

ObjectiveOsteoarthritis (OA) is the most common form of arthritis and the leading cause of disability in the elderly. Of all the joints, genetic predisposition is strongest for OA of the...

The autocrine role of proteoglycan-4 (PRG4) in modulating osteoarthritic synoviocyte proliferation and expression of matrix degrading enzymes

BackgroundLubricin/proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. Recently, we showed that recombinant human PRG4 (rhPRG4) is a putative ligand for CD44 receptor. rhPRG4-CD44 interaction inhibits cytokine-induced rheumatoid arthritis synoviocyte proliferation. The objective of this study is to decipher the autocrine function of PRG4 in regulating osteoarthritic synoviocyte proliferation and expression of catabolic and pro-inflammatory mediators under basal and interleukin-1 beta (IL-1β)-stimulated conditions.MethodsCytosolic and nuclear levels of nuclear factor kappa B (NFκB) p50 and p65 subunits in Prg4+/+ and Prg4-/- synoviocytes were studied using western blot. Nuclear translocation of p50 and p65 proteins in osteoarthritis (OA) fibroblast-like synoviocytes (FLS) in response to IL-1β stimulation in the absence or presence of rhPRG4 was studied using DNA binding assays. OA synoviocyte (5000 cells per well) proliferation following IL-1β (20 ng/ml) treatment in the absence or presence of rhPRG4 (50–200 μg/ml) over 48 hours was determined using a colorimetric assay. Gene expression of matrix metalloproteinases (MMPs), tissue inhibitor of metallproteinases-1 (TIMP-1), TIMP-2, IL-1β, IL-6, IL-8, TNF-α, cycloxygenae-2 (COX2) and PRG4 in unstimulated and IL-1β (1 ng/ml)-stimulated OA synoviocytes, in the presence or absence of rhPRG4 (100 and 200 μg/ml), was studied following incubation for 24 hours.ResultsPrg4-/- synoviocytes contained higher nuclear p50 and p65 levels compared to Prg4+/+ synoviocytes (p < 0.05). rhPRG4 (100 μg/ml) reduced p50 and p65 nuclear levels in Prg4+/+ and Prg4-/- synoviocytes (p < 0.001). Similarly, rhPRG4 (200 μg/ml) inhibited NFκB translocation and cell proliferation in OA synoviocytes in a CD44-dependent manner (p < 0.001) via inhibition of IκBα phosphorylation. IL-1β reduced PRG4 expression in OA synoviocytes and rhPRG4 (100 μg/ml) treatment reversed this effect (p < 0.001). rhPRG4 (200 μg/ml) reduced basal gene expression of MMP-1, MMP-3, MMP-13, IL-6, IL-8, and PRG4 in OA synoviocytes, while increasing TIMP-2 and cycloxygenase-2 (COX2) expression (p < 0.001). rhPRG4 (200 μg/ml) reduced IL-1β induction of MMP-1, MMP-3, MMP-9, MMP-13, IL-6, IL-8, and COX2 expression in a CD44-dependent manner (p < 0.001).ConclusionPRG4 plays an important anti-inflammatory role in regulating OA synoviocyte proliferation and reduces basal and IL-1β-stimulated expression of catabolic mediators. Exogenous rhPRG4 autoregulates native PRG4 expression in OA synoviocytes.

Elevated erythrocyte sedimentation rate and high-sensitivity C-reactive protein in osteoarthritis of the knee: relationship with clinical findings and radiographic severity.

We assessed erythrocyte sedimentation rate and high-sensitivity C-reactive protein concentration in knee osteoarthritis and non-knee osteoarthritis. In addition, we investigated potential relationship between the levels of erythrocyte sedimentation rate and high-sensitivity C-reactive protein with clinical findings and radiographic severity. We compared erythrocyte sedimentation rate and high-sensitivity C-reactive protein concentration between 104 patients with knee osteoarthritis (knee osteoarthritis group; 25 males, 79 females; mean age, 73 y) and 50 patients without knee osteoarthritis (non-knee osteoarthritis group; 16 males, 34 females; mean age, 64 y) excluding any patients with comorbid joint osteoarthritis, rheumatoid arthritis, malignant tumours or inflammatory diseases. In the knee osteoarthritis group, we assessed whether erythrocyte sedimentation rate and high-sensitivity C-reactive protein concentration differed in clinical features and Kellgren-Lawrence (KL) grades. Erythrocyte sedimentation rate and high-sensitivity C-reactive protein were significantly higher in the knee osteoarthritis group than in the non-knee osteoarthritis group (P = 0.0013 and 0.00010, respectively). In the knee osteoarthritis group, erythrocyte sedimentation rate was significantly elevated in patients with tenderness and patellar ballottement (P = 0.032 and 0.038, respectively), and high-sensitivity C-reactive protein concentration was significantly elevated in patients with tenderness, swelling and patellar ballottement (P = 0.0042, 0.00030 and 0.019, respectively). Erythrocyte sedimentation rate in KL-I was lower than erythrocyte sedimentation rate in KL-III and -IV (P = 0.012 and 0.037, respectively). Erythrocyte sedimentation rate in KL-II did not significantly differ from erythrocyte sedimentation rate in the other groups. High-sensitivity C-reactive protein concentration was lower in grade I than in KL-II, -III and -IV (P = 0.044, 0.0085 and 0.049, respectively). Erythrocyte sedimentation rate and high-sensitivity C-reactive protein concentration were higher in patients with knee osteoarthritis and were related to clinical features. In knee osteoarthritis, high-sensitivity C-reactive protein concentration may increase in early-stage KL-II.

Apolipoprotein-A1 as a damage-associated molecular patterns protein in osteoarthritis: ex vivo and in vitro pro-inflammatory properties.

Osteoarthritis (OA) is associated with a local inflammatory process. Dyslipidemia is known to be an underlying cause for the development of OA. Therefore, lipid and inflammatory levels were quantified ex vivo in blood and synovial fluid of OA patients (n=29) and compared to those of rheumatoid arthritis (RA) patients (n=27) or healthy volunteers (HV) (n=35). The role of apolipoprotein A-I (ApoA1) was investigated in vitro on inflammatory parameters using human joint cells isolated from cartilage and synovial membrane obtained from OA patients after joint replacement. Cells were stimulated with ApoA1 in the presence or not of serum amyloid A (SAA) protein and/or lipoproteins (LDL and HDL) at physiological concentration observed in OA synovial fluid. In our ex vivo study, ApoA1, LDL-C and total cholesterol levels were strongly correlated to each other inside the OA joint cavity whereas same levels were not or weakly correlated to their corresponding serum levels. In OA synovial fluid, ApoA1 was not as strongly correlated to HDL as observed in OA serum or in RA synovial fluid, suggesting a dissociative level between ApoA1 and HDL in OA synovial fluid. In vitro, ApoA1 induced IL-6, MMP-1 and MMP-3 expression by primary chondrocytes and fibroblast-like synoviocytes through TLR4 receptor. HDL and LDL attenuated joint inflammatory response induced by ApoA1 and SAA in a ratio dependent manner. In conclusion, a dysregulated lipidic profile in the synovial fluid of OA patients was observed and was correlated with inflammatory parameters in the OA joint cavity. Pro-inflammatory properties of ApoA1 were confirmed in vitro.

Differential expression of COX-2 in osteoarthritis and rheumatoid arthritis

In this study, we investigated the differential expression profiles of cyclooxygenase-2 (COX-2) mRNA and proteins in osteoarthritis (OA) and rheumatoid arthritis (RA) patients to elucidate the role of COX-2 expression in the pathogenesis and development of these diseases and to provide novel drug targets for treating arthritis. A total of 60 patients who received arthroscopic surgeries for treating OA (N = 30) or RA (N = 30) were examined. Fifteen normal synovial tissue samples were included as the control group. Fibroblastic synovial cells in all samples were cultured in vitro and COX-2 mRNA, protein expression levels, and COX-2 levels were detected in synovial fluids by real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay methods, respectively. The mRNA level of COX-2 was significantly elevated in synovial cells from OA and RA patients compared to that in control samples (P < 0.05). COX-2 mRNA level was significantly higher in synovial cells from OA patients than in those from RA patients (P < 0.05). Consistent results were obtained for COX-2 protein expression levels from patients' synovial samples. In synovial fluids, OA (P < 0.05), but not RA (P > 0.05), patients showed significantly higher COX-2 levels compared to the control group. Elevated synovial COX-2 expression facilitates the pathogenesis of OA and RA, and thus this index reflects the condition of these 2 diseases.

Circulating C reactive protein in osteoarthritis: a systematic review and meta-analysis

BackgroundThere is emerging evidence that the development and progression of osteoarthritis (OA) is associated with inflammation. C reactive protein (CRP), a systemic marker for inflammation, may be elevated in OA...

Significance of C-reactive protein in osteoarthritis and total knee arthroplasty outcomes.

The relationship between systemic inflammatory processes to total knee arthroplasty (TKA) outcomes remains unclear. This study investigates the relationship between serum high-sensitivity C-reactive protein (hs-CRP) and functional outcomes post-TKA. A total of 31 patients with osteoarthritis (OA) who underwent TKA were enrolled in the study; 15 with hs-CRP ≤1.0 mg/l (low hs-CRP group) and 16 subjects with hs-CRP ≥4.0 mg/l (high hs-CRP group). During surgery, synovium and bone sections were sequestered, formalin-fixed, and paraffin embedded for slide preparation. Tissue sections were stained with hematoxylin and eosin and analyzed using a light microscope. A total of 12 cytokines were measured in synovial fluid samples from the knee joint at time of surgery and analyzed using the Luminex Multi-Analyte Profiling System. Relationships between cytokines and hs-CRP were assessed using Spearman correlation coefficients. Student's t-tests were used to compare Short Form health outcomes survey (SF-12) health outcomes between high and low hs-CRP, and presurgical and postsurgical visits. Mean ± standard deviation (SD) baseline and 1-year hs-CRP values for the low hs-CRP group were 0.55 ± 0.23 mg/l and 1.22 ± 1.32 mg/l, respectively (n = 15; p = 0.051) and for the high hs-CRP group were 7.86 ± 5.98 mg/l and 14.11 ± 38.9 mg/l, respectively (n = 13; p = 0.54). Lymphocytes were present in 10 synovium and one bone sample (all but one from high hs-CRP group). Interleukin (IL)-5 and IL-10 were significantly correlated with hs-CRP (p = 0.0137 and p = 0.0029, respectively). The low hs-CRP group exhibited significant improvement in the physical component of SF-12 at 6 and 12 months compared with baseline, whereas the high hs-CRP group exhibited significant improvement only at 6 months. Body mass index (BMI) had a significant positive correlation with presurgical hs-CRP. The results of this study provide support for inflammatory mechanisms contributing to the OA progression, with hs-CRP being a possible predictive variable, combined with BMI and other comorbidities, of post-TKA function.

Regulatory Functions of Insulin-like Growth Factor Binding Proteins in Osteoarthritis

Insulin-like growth factor binding proteins (IGFBPs) are a group of secreted proteins, which bind to IGF-I (and IGF-II) with high affinity and modulate the biological actions of IGFs. Abundant evidence points the importance of the IGF-I/IGFBP system on both cell growth and differentiation. A role for the IGF-I/IGFBP system in the regulation of normal human cartilage has been previously reported. In this context, recent studies suggest an emerging role for IGFBPs in the failure of cartilage during osteoarthritis (OA). Indeed, increased IGFBP levels have been reported in both the articular cartilage and synovial fluid from patients with OA. Overexpression of IGFBPs, by altering the bioavailability and function of IGFs, is likely to deliver IGFs-independent signals for chondrocyte survival. This, at least in part, might explain the degenerative changes of the cartilage in OA. Further studies are necessary to clarify the mechanisms that cause the overexpression of IGFBPs in patients with OA. Advances in our understanding of the relationship between osteoarthritis and the IGF-I/IGFBP system may lead to new treatment strategies for this degenerative disease.

Investigation of serum C-reactive protein in osteoarthritis of the knee

Investigation of serum C-reactive protein in osteoarthritis of the knee