Serum levels of cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee osteoarthritis

180

118

Objective. To assess whether the association of genetic polymorphisms with osteoarthritis (OA) in other populations could be replicated in a large, multicenter, mixed-sex, case-control study of clinical knee OA.Methods. Genetic polymorphisms in OA candidate genes were genotyped in 298 men and 305 women, ages 50-86 years, all of whom had a diagnosis of knee OA as assessed clinically and radiographically, and in 300 male and 299 female control subjects matched for age and ethnicity. Allele and haplotype frequencies for 5 genes (ASPN, CALM1, COL2A1, COMP, and FRZB) previously tested for association with hip and/or knee OA in other populations were compared between patients and control subjects, analyzing men and women separately.Results. The same FRZB 2-marker single-nucleotide polymorphism (SNP) haplotype associated with hip OA in other populations of Caucasian women was shown to increase the risk of knee OA among the women (but not the men) in the current study (odds ratio [OR] 2.87, P < 0.04). The CALM1 SNP, which affects the risk of hip OA in Japanese individuals, was not shown to be associated with susceptibility to OA in men or women. COL2A1 haplotypes were demonstrated to be associated with a decreased risk of knee OA in men (OR 0.68, P < 0.005) but not in women. COMP haplotypes that were associated with susceptibility to knee OA were different in men and women (P < 0.014 and P < 0.032, respectively). A meta-analysis of these data and those from previously published reports indicated a strong association between the FRZB G324 allele (P < 0.0003) and suggested that an ASPN allele is protective against the risk of knee OA in Caucasians (P < 0.02).Conclusion. Our results indicate that genetic polymorphisms affecting knee OA vary between populations (Japanese versus Caucasian) and sexes and indicate a role for ASPN, COMP, FRZB, and COL2A1 in Caucasians.

Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee

Valdes

Loughlin

Oene

et al. 2007

180

118

“…Conflicting associations were found for the level of keratan sulfate and the level of cartilage oligomeric matrix protein (COMP). With regard to COMP, Bruyere et al (42) found no significant association (OR or P value not provided) in contrast to Sharif et al (24) and Vilim et al (16). Bruyere et al (42) found no significant associations between osteocalcin, pyridinoline, or deoxypyridinoline and progression of knee OA (OR or P values not provided).…”

Section: Resultsmentioning

confidence: 97%

Prognostic factors of progression of osteoarthritis of the knee: A systematic review of observational studies

Belo¹,

Berger²,

Reijman³

et al. 2007

167

132

Objective. To provide an overview of prognostic factors of knee osteoarthritis (OA) progression. Methods. We searched Medline and Embase up to December 2003 according to a specified search strategy (keywords for disease, location, and study design). Studies that fulfilled predefined criteria were assessed for methodologic quality. Study characteristics and associations were extracted and the results were summarized according to a best evidence synthesis. Results. Of the 1,004 studies found, 37 met the inclusion criteria. Methodologic quality was assessed and only highquality studies were included (n ‫؍‬ 36). The best evidence synthesis yielded strong evidence that hyaluronic acid serum levels and generalized OA are predictive for progression of knee OA. Sex, knee pain, radiologic severity, knee injury, quadriceps strength, and regular sport activities were not predictive. Conflicting evidence for associations was found for several factors including body mass index and age. Limited evidence for an association with progression of knee OA was found for several factors, including the alignment (varus/valgus) of the joint. Limited evidence for no association with progression of OA was also found for several factors, including meniscectomy, several markers of bone or cartilage turnover, and the clinical diagnosis of localized OA. Conclusion. Generalized OA and level of hyaluronic acid seem to be associated with the radiologic progression of knee OA. Knee pain, radiologic severity at baseline, sex, quadriceps strength, knee injury, and regular sport activities seem not to be related. For other factors, the evidence was limited or conflicting.

“…as well as in animal models (26,27). We measured serum COMP levels in the experimental groups at 2 weeks and 10 weeks postsurgery (Figure 2a).…”

Section: Resultsmentioning

confidence: 99%

The role of subchondral bone remodeling in osteoarthritis: Reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model

Hayami

Pickarski

Wesolowski

et al. 2004

514

466

Objective. It has been suggested that subchondral bone remodeling plays a role in the progression of osteoarthritis (OA). To test this hypothesis, we characterized the changes in the rat anterior cruciate ligament transection (ACLT) model of OA and evaluated the effects of alendronate (ALN), a potent inhibitor of bone resorption, on cartilage degradation and on osteophyte formation.Methods. Male Sprague-Dawley rats underwent ACLT or sham operation of the right knee. Animals were then treated with ALN (0.03 and 0.24 g/kg/week subcutaneously) and necropsied at 2 or 10 weeks postsurgery. OA changes were evaluated. Subchondral bone volume and osteophyte area were measured by histomorphometric analysis. Coimmunostaining for transforming growth factor ␤ (TGF␤), matrix metalloproteinase 9 (MMP-9), and MMP-13 was performed to investigate the effect of ALN on local activation of TGF␤.Results. ALN was chondroprotective at both dosages, as determined by histologic criteria and collagen degradation markers. ALN suppressed subchondral bone resorption, which was markedly increased 2 weeks postsurgery, and prevented the subsequent increase in bone formation 10 weeks postsurgery, in the untreated tibial plateau of ACLT joints. Furthermore, ALN reduced the incidence and area of osteophytes in a dosedependent manner. ALN also inhibited vascular invasion into the calcified cartilage in rats with OA and blocked osteoclast recruitment to subchondral bone and osteophytes. ALN treatment reduced the local release of active TGF␤, possibly via inhibition of MMP-13 expression in articular cartilage and MMP-9 expression in subchondral bone. Conclusion. Subchondral bone remodeling plays an important role in the pathogenesis of OA. ALN or other inhibitors of bone resorption could potentially be used as disease-modifying agents in the treatment of OA.Osteoarthritis (OA) is a degenerative joint disease characterized by pain, cartilage loss, and joint stiffness. Although OA has long been considered to be primarily a cartilage disorder associated with focal articular cartilage degradation, this disease is accompanied by well-defined changes in the subchondral and periarticular bone, including sclerosis and cyst and osteophyte formation (1). The importance of the bone changes in the initiation and progression of OA is still being debated. It has been suggested that increased subchondral bone stiffness reduces the ability to dissipate the load and distribute the strain generated within the joint. This increases peak dynamic forces in the overlying articular cartilage and can accelerate its damage over time (2). The functional integrity of the articular cartilage can therefore depend on the mechanical properties of the underlying bone. Accordingly, cartilage damage leads to full-thickness cartilage loss only upon repetitive loading over an already stiffened subchondral bone plate (3).Recent studies have demonstrated increased subchondral bone turnover accompanied by specific architectural changes in the subchondral trabecular bone in OA joints (4,5...