Osteoclast differentiation factor

YAMAGISHI T, OTSUKA E and HAGIWARA H (2001) Reciprocal control of expression of mRNAs for osteoclast differentiation factor and OPG in osteogenic stromal cells by genistein evidence for the involvement of topoisomerase 11 in osteoclastogenesis. Endocrinol 142, 3632-7. 

Nakagawa N, Kinosaki M, Yamaguchi K, Shima N, Yasuda H, Yano K, Morinaga T, Hi-gashio K (1998) RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis. BioChem Biophys Res Commun 253 395-400... 

Gao YH, Shinki T, YuasaT, Kataoka-Enomoto H, Komori T, Suda T, Yamaguchi A (1998) Potential role of cbfal, an essential transcriptional factor for osteoblast differentiation, in osteoclastogenesis regulation of mRNA expression of osteoclast differentiation factor (ODF). BioChem Biophys Res Commun 252 697-702... 

Osteoblasts around bony microcracks are induced to express two cytokines monocyte Colony Stimulating Factor (mCSF) which is secreted and Osteoclast Differentiating Factor (ODF) which is mainly on the cell surface. The mCSF stimulates microcrack-adherent monocytes to proliferate and fuse into large multinucleated cells (preosteoclasts) that express Osteoclast Differentiation and Activation Receptor (ODAR). 

Fig. 10.5 Osteoclast differentiation factors. Osteoblasts make monocyte colony stimulating factor (mCSF) that induces bone adherent monocytes carrying the corresponding receptor (mCSF Receptor) to fuse into osteoclast precursors (preosteoclasts). Preosteoclasts develop within the periosteum and are detectable by their expression of the osteoclast differentiation and activation receptor (ODAR). Osteoblasts also make cell-membrane bound and soluble osteoclast differentiation factors (ODF and sODF) that react with ODAR to cause preosteoclast differentiation. Finally, osteoblasts make osteoclast inhibition factor (OCIF), also called osteoprotegerin, which acts as an ODF decoy receptor and prevents ODF or sODF reacting with ODAR. ODAR is commonly referred to as RANK and ODF as the RANK ligand (RANKL) in the literature (see text)...

Osteoclast differentiation factor RANK ligand Osteoprotegerin ligand TNF-related activation-induced cytokine... 

Jimi, E., Akiyama, S., Tsurukai, T., Okahashi, N., and Kobayashi, K. (1999). Osteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function. /. Immunol. 163, 434-442. 

Interleukin 1 (IL-1) is produced mainly by activated monocytes-macropha-ges, and its principal action is to stimulate thymocytes. A pleiotropic cytokine, IL-1 induces the expression of a large diversity of cytokines such as IL-6, leukaemia inhibitory factor (LIF), and other proinflammatory molecules (Di-marello 1994). IL-1 and TNF-a carry out as part of their function increasing the expression of NF-/cB and JNK (c-Jun N-terminal kinase). The importance of IL-1 in OCS is demonstrated because the IL-1-receptor-deficient mouse is resistant to ovariectomy (OVX)-induced bone loss (Lorenzo et al. 1998). The importance in pathological bone loss is also illustrated by the fact that treatment with IL-1 receptor antagonist slows down bone erosion for patients affected with rheumatoid arthritis (Kwan et al. 2004). IL-1 increases osteoclast differentiation rather than mature osteoclast activity, and infusion of IL-1 into mice induces hypercalcemia and bone resorption. Finally, IL-1 and TNF-a... 

Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ (1999) Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 20 345-357... 

Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E, Tan HL, Elliott G, Kelley MJ, Sarosi I, Wang L, Xia XZ, Elliott R, Chiu L, Black T, Scully S, Capparelli C, Morony S, Shimamoto G, Bass MB, Boyle WJ (1999) Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci USA 96 3540-3545... 

Quinn JM, Itoh K, Udagawa N, Hausler K, Yasuda H, Shima N, Mizuno A, Higashio K, Takahashi N, Suda T, Martin TJ, Gillespie MT (2001) Transforming growth factor beta affects osteoclast differentiation via direct and indirect actions. J Bone Miner Res 16 1787-1794... 

Recently, two products of the osteoblast have been identified that appear to be the final common pathway in coordinating osteoblast and osteoclast activity. The first, receptor activator of nuclear factor-KB (RANK) ligand, binds to a receptor on osteoclast progenitor cells and increases osteoclast differentiation and activity. The second, osteo-protegerin (OPG), serves as a decoy receptor for RANK ligand. When OPG binds to RANK ligand, the osteoclast-stimulation activity is prevented. The relative ratios of these two molecules determine bone turnover. 

Bones are constantly dissolved by osteoclasts and remineralized by osteoblasts in response to mechanical forces. Osteoclasts possess an acidic compartment and pass demineralized bone products to the periosteum (Sect. 1). They develop in stress-induced bony microcracks and are activated by differentiation factors secreted by osteoblasts, especially after menopause. Menopausal osteoporosis is controlled by drugs that are a stable form of pyrophosphate (bisphosphonate) or cathepsin K inhibitors (Sect. 2). The calcium ion concentration of blood is raised by parathyroid hormone and a vitamin D derivative called calcitriol. Parathyroid hormone causes kidneys to excrete phosphate, retain calcium, and activate calcitriol production (Sect. 3). Calcitriol induces calcium transporter proteins in osteoclasts and intestinal epithelium, where they move calcium from bone or diet into blood (Sect. 4). The chapter concludes with a discussion of calcitonin which lowers blood calcium concentrations by reversing parathyroid hormone effects on the kidney and inhibiting osteoclast activity (Sect. 5). 

Osteoprotegerin, a secreted protein of the tumor necrosis factor family that inhibits osteoclast differentiation and activation, has been shown to protect against warfarin-induced calcification in rats. ... 

During bone formation, a series of sequential changes occur in cells in the osteoblast lineage, including osteoblast chemotaxis, proliferation and differentiation, which in turn is followed by formation of mineralised bone and cessation of osteoblast activity. The osteoblast changes are preceded by osteoclast apoptosis, which may be dependent on active TGF- 3 released from the resorbed bone. This is followed by chemotactic attraction of osteoblasts or their precursors to the sites of the resorption defect. Chemotactic attraction of osteoblast precursors is likely mediated by local factors produced during the resorption process. 

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