Osteoblasts and osteoclasts in bone remodeling and inflammation.
Bone homeostasis is maintained by a balance between bone resorption by osteoclasts and bone formation by osteoblasts. Osteoblasts not only play a central role in bone formation by synthesizing multiple bone matrix proteins, but regulate osteoclast maturation by soluble factors and cognate interaction, resulting in bone resorption. Osteoclast maturation requires stimulation by RANKL expressed on osteoblasts, and the cognate interaction is mediated by firm adhesion via ICAM-1. During the processes, pro-inflammatory cytokines such as IL-1 and TNF-alpha, cause an imbalance in bone metabolism, by favoring bone resorption via the induction of RANKL and ICAM-1 on osteoblasts. These inflammatory signals originate from the immune system, the largest source of cell-derived regulatory signals, and such immunological signals to the bone are transmitted primarily via osteoblasts to induce osteoclast maturation, resulting in secondary osteoporosis. Actually, such phenomena mainly occur at the interface between proliferating synovium and bone tissue in rheumatoid arthritis (RA). Thus, therapeutic strategies for these conditions, an anti-TNF-alpha antibody and an IL-1 receptor antagonist, effective for treating RA disease activity, also reduce secondary osteoporosis and joint destruction. Based on an improved understanding of immune signals, investigation of the suppression of cell functions may lead to improved understanding and better treatment of diseases of bone metabolism and osteoporosis.
Tanaka
Yoshiya
Y
First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu 807-8555, Japan. tanaka@med.uoeh-u.ac.jp
Nakayamada
Shingo
S
Okada
Yosuke
Y
D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D010006:Osteoblasts / Q000473:pathology / Q000502:physiology*; D010010:Osteoclasts / Q000473:pathology / Q000502:physiology*; D010024:Osteoporosis / Q000473:pathology