Role of Secreted Frizzled-Related Protein 1 and Tumor Necrosis Factor-α (TNF-α) in Bone Loss of Patients with Rheumatoid Arthritis

Abstract

Bone loss is one of the emerging extra-articular manifestations of rheumatoid arthritis. TNF-α is the main inflammatory cytokine that can directly increase bone resorption. However, its role in bone formation is still unknown, especially related to secreted frizzled-related protein 1 (SFRP-1), an osteoblast inhibitor. This study examines the correlation between TNF-α and SFRP-1, with a bone turn over marker (CTX and P1NP). This is a cross-sectional study with 38 subjects of premenopausal female patients with RA. This study found that 60.6% of the patients were in remission or low disease activity. The median of TNF-α was 10.6 pg/mL, mean of SFRP-1 was 9.29 ng/mL, mean of CTX was 2.74 ng/mL, and the median of P1NP was 34.04 pg/ml. There is positive correlation between TNF-α and P1NP (r = 0:363, p = 0:026), also between SFRP-1 and P1NP (r = 0:341; p = 0:036). A low level of TNF-?, high level of SFRP-1, high level of CTX, and low level of P1NP in this study indicate a high bone turn over process, with dominant resorption activity in premenopausal female patients with RA.

Osteoblast role in the pathogenesis of rheumatoid arthritis

“…IL17, in physiological conditions, is involved in defending epithelia and mucous membranes against bacteria and fungi, but it is overexpressed and seems to play an important role in inflammatory diseases like RA and spondyloarthritis (SpA); it was suggested that IL17-A is involved in the alteration of bone homeostasis in inflammatory arthritis by acting on osteoclast and osteoblast related pathways. In vitro stimulation of osteoblasts with IL17-A enhances sFRP1, a Wnt pathway antagonist, inhibiting osteoblasts formation [ 98 ]. Actually, the effects of IL17-A on osteoblasts in in vitro models are not always homogeneous [ 99 ], and the role of IL17 family in bone remodeling is still not clear and needs for further investigations, but its overexpression in pathologic conditions is harmful to bone homeostasis.…”

SFRP1 Negatively Modulates Pyroptosis of Fibroblast‐Like Synoviocytes in Rheumatoid Arthritis: A Review

“…Therefore, SFRP1 is considered a Wnt signaling pathway antagonist, which in turn interfere with Wnt signaling transduction and plays an important role in determining cell fate by regulating cell proliferation, differentiation, apoptosis, and pyroptosis ( 11 ). This regulation has also been studied in RA-FLS ( 12 ). In addition, some studies have found that SFRP1 can bind to recombinant A disintegrin and metalloproteinase 10 (ADAM10) protein and downregulate its activity in the Notch signaling transduction pathway, thus blocking the activation of Notch signaling ( 13 ).…”