Exploring the link between bone biomarkers and proinflammatory cytokines in patients with osteoarthritis

Background Osteoarthritis is multifactorial joint disorder marked by the progressive breakdown of articular cartilage, alterations in the underlying subchondral bone, and chronic inflammation of the synovial membrane.
Objective To measure serum levels of bone biomarkers (osteocalcin and sclerostin) in osteoarthritis patients as compared to healthy controls and also to find out the link of these biomarkers with proinflammatory cytokines including IL-6, IL-17, IL-1β and TNF-α.
Materials and methods A case-control study was implemented on 65 osteoarthritis patients and 35 healthy controls participants. Blood samples were taken from participants after obtaining written informed consent. Serum levels of cytokines and bone markers were measured using ELISA. Pain disability and intensity were measured using the "Chronic Pain Grade questionnaire".
Results Compared to controls, patients with osteoarthritis had significantly higher levels of IL-1β, TNF-α, IL-6, and IL-17 (P < 0.0001 for all). Osteocalcin levels were dramatically lower in the osteoarthritis group than the controls (mean ± SD: 23.50 ± 19.30 ng/mL vs. controls 48.90 ± 5.20 ng/mL), while sclerostin levels were much higher (11.70 ± 1.10 ng/mL in osteoarthritis vs. 3.80 ± 0.90 ng/mL in controls, P < 0.0001). Osteocalcin showed a moderate positive correlation with IL-17, IL-6, and TNF-α; sclerostin showed a negative correlation with these cytokines.
Discussion A strong positive correlation exists between osteocalcin and proinflammatory interleukins. The  downregulation of sclerostin in OA also shares common pathways with proinflammatory cytokines that drive expression of osteocalcin. Inflammation results in osteocyte apoptosis or their dedifferentiation, and  this further lowers the population of sclerostin-secreting cells in the subchondral bone. This is how the reverse correlation is explained between sclerostin and proinflammatory cytokines in OA.
Conclusions Results show a robust inflammatory-bone axis in the pathogenesis of osteoarthritis. High proinflammatory cytokines might bring about osteocalcin expression and also inhibit sclerostin, leading to pathological subchondral bone alteration. These biomarkers reflect disease activity and therefore could be used for early detection as well as monitoring and phenotypic stratification of osteoarthritis.

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