Human osteoclast formation and bone resorption by monocytes and synovial macrophages in rheumatoid arthritis.

Abstract

(1,25(OH)2D3)'9-22; the mononuclear and multinucleated cells formed in these cocultures show all the phenotypic characteristics of osteoclasts, including expression of tartrate resistant acid phosphatase (TRAP), calcitonin receptors (CTR), and most importantly, the functional ability to produce resorption lacunae in bone. In the context of an inflammatory disease such as rheumatoid arthritis, where there is a heavy macrophage infiltrate in synovial tissues, osteoclast differentiation by monocytes and macrophages could represent an important mechanism for the pathogenesis of bone destruction. In this study we have sought to determine whether this cellular mechanism of osteoclast formation and pathological bone resorption operates in rheumatoid arthritis. Peripheral blood monocytes and synovial macrophages from rheumatoid arthritis patients were co-cultured with osteoblastic cells in the presence and absence of humoral factors which are known to be important in mouse osteoclast formation, in order to determine the cellular and humoral conditions for mononuclear phagocyte-osteoclast differentiation in rheumatoid arthritis.2'25

Regulation of bone destruction in rheumatoid arthritis through RANKL-RANK pathways

“…We also demonstrated that peripheral monocytes can differentiate into osteoclast-like cells when co-cultured with synovial fibroblasts obtained from RA synovial tissues in the presence of 1,25(OH)2D3 and M-CSF. Similar results were reported by Fujikawa et al [17] . They found that synovial macrophages isolated from RA synovial tissues can differentiate into osteoclast-like cells when co-cultured with UMR 106 rat osteoblast-like cells.…”

Histone deacetylases (HDAC) in physiological and pathological bone remodelling

“…Excessive osteoclast-associated bone resorption is a characteristic feature in RA with studies demonstrating that osteoclast knock out mice are resistant to arthritis-induced bone loss [93,94]. Enhanced osteoclast formation has also been demonstrated in human RA synovial tissues [40,[95][96][97]. In animal models of inflammatory arthritis and in human RA tissues, large multinucleated osteoclastic cells that resorb the subchondral bone, have been detected at sites of bone loss in synovial joints [40,[95][96][97].…”

Development of an ex vivo cellular model of rheumatoid arthritis: Critical role of cd14‐positive monocyte/macrophages in the development of pannus tissue

“…Osteoclasts are associated with bone destruction in RA joints (6). Their origin in rheumatoid joints has not yet been identified, but findings of previous studies have indicated that bone marrow-derived CD14-positive cells are responsible for the development of osteoclasts and that both monocytes and dendritic cells can differentiate into functional osteoclasts (7)(8)(9)(10). Osteoclast formation requires cellcell interaction between osteoblasts and osteoclast precursors in bone remodeling.…”