Expression of osteopontin at sites of bone erosion in a murine experimental arthritis model of collagen‐induced arthritis: Possible involvement of osteopontin in bone destruction in arthritis

Abstract

Objective. To investigate the involvement of osteopontin (OPN) in bone destruction in a murine experimental arthritis model of collagen-induced arthritis (CIA).Methods. The expression of OPN was examined at both the messenger RNA (mRNA) and protein levels in various arthritic lesions in mice with CIA by in situ hybridization and immunohistochemistry, respectively. In addition, the expression of ␣v␤3 integrin, a receptor for OPN, the ligation of which is thought to be essential for bone resorption by osteoclasts, was examined by immunohistochemistry. Plasma concentrations of OPN were measured at different time points in the course of CIA by enzyme-linked immunosorbent assay.Results. OPN mRNA was detected mainly at sites of bone erosion in arthritic lesions, where activated osteoclasts were present; OPN protein was also detected at sites of bone erosion. In the arthritic synovium, OPN was predominantly expressed in the synovial lining layer, but not in lymphoid aggregates. In addition, ␣v␤3 integrin was detected coincident with OPN at sites of bone erosion (bone-pannus junction). Plasma OPN levels were markedly elevated at the time points that corresponded to arthritis flares, and higher levels were maintained during the progression of arthritis.Conclusion. OPN may mediate bone resorption by osteoclasts in arthritis through ligation with its receptor, ␣v␤3 integrin. OPN may be a useful therapeutic target molecule in the prevention of bone destruction in arthritis.

Osteopontin Is Associated with Increased Arterial Stiffness in Rheumatoid Arthritis

“…Considering the known properties of OPN as a regulator of inflammation and bone destruction in RA (26,27,41), we suggest that OPN might be a point of contact between inflammation and the consequent articular damage and atherosclerosis in RA. The observed lower OPN levels of non-case and healthy donors led us to speculate that this inflammatory and plaque destabilizing protein is peculiar in RA pathogenesis.…”

“…On the other hand, this cytokine is expressed in chronic inflamma-tory and autoimmune diseases (20)(21)(22)(23)(24)(25) with proinflammatory functions, and it has been suggested as a potential mediator of the promotion of joint destruction in RA (26). Enhanced levels of OPN mRNA and protein were found in synovial tissue from RA patients (27). Moreover, OPN deficiency has been shown to protect joints against destruction in arthritis-induced mice-suppressing articular destruction, chondrocyte apoptosis, and synovial angiogenesis (28), suggesting a direct role in bone readsorption beyond its effects on inflammation (29).…”

Essential role of the cryptic epitope SLAYGLR within osteopontin in a murine model of rheumatoid arthritis

“…Bone resorption by osteoclasts is regulated by the interaction of αvβ3 integrin on osteoclasts and OPN (39). Indeed, we recently found that OPN and its receptor αvβ3 integrin were coexpressed by activated osteoclasts at the site of bone erosion (10).…”

“…Anti-TNF-α antibody and IL-1 receptor antagonist are effective in the prevention of both inflammation and joint erosion in early active RA; however, they are unable to completely stop the progression of joint destruction in patients with RA, indicating that the pathological process of RA is complex and that other factors are critically involved (2)(3)(4)(5). Osteopontin (OPN) has been suggested as potential mediator of the promotion of joint destruction in patients with RA through the αvβ3 and αvβ5 integrins expressed on osteoclasts and chondrocytes (6)(7)(8)(9)(10)(11). OPN is an extracellular matrix protein containing an Arg-Gly-Asp (RGD) sequence and upregulated in activated T cells, macrophages, invading synoviocytes, and articular chondrocytes associated with inflammation and tissue repair (12)(13)(14).…”

Celastrus and Its Bioactive Celastrol Protect against Bone Damage in Autoimmune Arthritis by Modulating Osteoimmune Cross-talk

“…Other mediators, such as osteopontin (OPN), osteocalcin (OCN) and insulin-like growth factor (IGF)-I also influence bone remodeling. OPN is an extracellular matrix protein that is expressed in both synovial cells and chondrocytes in RA, and it can mediate bone resorption by osteoclasts (27). OCN is the most abundant noncollagenous protein of bone, and it is an indicator of osteoblastic activity (28).…”