Increased level of cytokines and matrix metalloproteinases in osteoarthritic subchondral bone

What Is the Utility of Biomarkers for Assessing the Pathophysiology of Hip Osteoarthritis? A Systematic Review

“…In three studies [19,22,37], uCTX-II levels were elevated in patients with hip OA 1.3 to 3.1 times that of the control group with associated effect size (d) of 2.2 to 3.7. Serum CRP level was elevated in patients with hip OA compared with control subjects in two studies (2.1-8.2 times greater than control levels, d 1.0-28.7) [11,21] while failing to demonstrate an effect in another study [27]. Thirteen other biomarkers demonstrated differences in levels between OA and control patients in a single study (with approximately 70% demonstrating large effect sizes).…”

“…A total of 16 different biomarkers demonstrated differences between patients with hip OA and non-OA control subjects (Table 2) Although most biomarkers were assessed in only one ''diagnosis'' study, urinary level of type II collagen telopeptide (uCTX-II) [19,22,37] and serum C-reactive protein (CRP) [11,21,27] levels both were increased in patients with hip OA in more than one study. In three studies [19,22,37], uCTX-II levels were elevated in patients with hip OA 1.3 to 3.1 times that of the control group with associated effect size (d) of 2.2 to 3.7.…”

The role of proteases in pathologies of the synovial joint

“…Both rheumatoid and osteoarthritis display inflammatory properties and are associated with the production of cytokines such as tumour necrosis factor (TNF) and interleukin-1 (IL-1) (Brennan, Maini, & Feldmann, 1992;Deleuran et al, 1992;Fernandes, Martel-Pelletier, & Pelletier, 2002;Hulejová et al, 2007). A number of cytokines are known to exist within tissues in inactive or sequestered forms that can be cleaved by proteases to generate functionally active forms.…”

“…In rheumatoid arthritis synovitis is associated with hyperplasia of the synoviocytes, an infiltration of mononuclear cells including B cells, T cells and macrophages into the synovial sublining, and the formation of a locally invasive pannus (Lee & Weinblatt, 2001). A number of studies have shown that in arthritic pathologies the synovial expression of a number of proteases, including MMP collagenases, ADAMTS aggrecanases and MMP-3, is increased as are the levels of these proteases in the synovial fluid (Hulejová et al, 2007;Smeets et al, 2003;Tchetverikov et al, 2004;Vankemmelbeke et al, 2001;Vankemmelbeke, Ilic, Handley, Knight, & Buttle, 1999). In vitro studies have implicated synovium-derived factors, in particular proinflammatory cytokines (Fell & Jubb, 1977;Saklatvala, Pilsworth, Sarsfield, Gavrilovic, & Heath, 1984) and proteases (Vankemmelbeke et al, 1999(Vankemmelbeke et al, , 2001) as mediators of cartilage destruction.…”

Knee osteoarthritis a pathological basis for use of newer drug therapies

“…38 The subchondral bone contributes to OA due to a defect in its role as a shock absorber; abnormal osteocyte function or increased production of bone-derived products, cytokines, and MMPs. 18,39 Bone marrow lesions have been found to be more common in persons with painful knees compared with persons with no knee pain and are related to pain severity. 40 …”