Basic cellular andmolecular principles of bone remodelling in rheumatoid arthritis
O. Kryštůfková; Š. Růžičková; J. Niederlová; J. Vencovský
Revmatologický ústav, Praha
Čes. Revmatol., , 2004, No. 1, p. 3-13.
Rheumatoid arthritis (RA) is a chronic, inflammatory and destructive joint disorder with progressivecourse, which results in functional limitation, physical disability as well as in extra-articularand systemic manifestations. Besides the soft tissue changes associated with synovitis, bone remodellingis also altered by local and systemic effects of inflammatory process. Activated osteoclastsare responsible for majority of bone resorption followed by focal erosions, juxta-articular and diffuseosteoporosis. Osteoresorption is up-regulated by bone-resorbing factors, which do not affect differentiationand activation of osteoclasts directly, but rather affect osteoblast activation. Osteoblaststhan produce molecules regulating osteoclastogenesis – osteoprotegerin (OPG) and receptor activatorof nuclear factor kappa B ligand (RANKL). The balance between resorption and formation ofbone is regulated by relative concentrations of these molecules in the local bone microenvironment.RANKL binds to RANK on the surface of osteoclast precursors and after growth factor M-CSFcontribution causes osteoclasts to differentiate and become activated. Osteoprotegerin modulatesosteoclastogenesis by competitive inhibition ofRANK/RANKLinteraction, which induces inhibitionof osteoclast activation and subsequently reduces their survival. This process is regulated byinflamed synovial cells (T cells, macrophages and fibroblast like cells). Osteoclastogenesis is associatedwith osteoblastogenesis through three key molecules RANKL, RANK and OPG. IncreasedRANKL/OPG ratio induces osteoresorption and results in bone destruction. One of the possibletherapeutic targets to reduce observed bone destruction is RANKL inhibition by natural inhibitor– OPG.
rheumatoid arthritis, osteoprotegerin, RANK, RANKL, bone resorption, osteoclastogenesis
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