Osteoclastogenesis inhibition

Fig. 7.3. Osteoclastogenesis after estrogen deficiency. Estrogen deprivation leads to an increase in the synthesis of RANKL for stromal/OB cells of the BM. This increase in the expression of RANKL leads to an increase in OCS. Estrogen deficiency also induces the synthesis and secretion of cytokines, such as IL-6 and M-CSF, that increase the number of preosteoclasts in the BM, and thus increases OCS. Nonetheless, certain cells of the immune system, such as monocytes and T-cells, intervene in the process when the supply of estrogens fails. These cells secrete IL-1 and TNF-a that are powerful inductors of OCS. When estrogens or agonists of estrogen receptors like raloxifene are administered, the synthesis and secretion of many of the mentioned cytokines diminish and the synthesis and liberation of OPG and TGF-/S are stimulated. These molecules inhibit OCS by inhibiting the RANKL/RANK signal pathway and by promoting osteoclast apoptosis...

Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG) a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139 1329-1337... 

Kwon BS, Wang S, Udagawa N, Haridas V, Lee ZH, Kim KK, Oh KO, Greene J, Li Y, Su J, Gentz R, Aggarwal BB, Ni J (1998) TR1, a new member of the tumor necrosis factor receptor superfamily, induces fibroblast proliferation and inhibits osteoclastogenesis and bone resorption. FASEB J 12 845-854... 

Murakami T, Yamamoto M, Ono K, Nishikawa M, Nagata N, Motoyoshi K, Akatsu T (1998) Transforming growth factor-betal increases mRNA levels of osteoclastogenesis inhibitory factor in osteoblastic/stromal cells and inhibits the survival of murine osteoclast-like cells. Biochem Biophys Res Commun 252 747-752... 

Y3. Yasuda, H., Shima, N., Nakagawa, N., Mochizuki, S. I., Yano, K., et al., Identity of osteoclasto-genesis inhibitory factor (OCIF) and osteoprotegerin (OPG) A mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139, 1329—1337 (1998). 

INTERLEUKIN-11 Interleukin-11 is a 23 kDa cytokine that stimulates hematopoiesis, intestinal epithelial ceU growth, and osteoclastogenesis and inhibits adipogenesis. IL-11 enhances megakaryocyte maturation. 

Regulates specific immunity and bone turnover binds to RANK receptor stimulates naive T cell proliferation promotes survival of RANK -t-T cells regulates T cell-dependent immune response binds to OPG inhibits osteoclastogenesis and leads to excess accumulation of bone and cartilage Binds to RANKL... 

Symbioimine inhibited osteoclastogenesis in the marine monocytic cell hne RAW264, with an EC50 of approximately 120 pM, bnt showed no cytotoxicity to these cells at 265 pM [40], Significant inhibition of purified cyclooxygenase 2, bnt not cyclooxygenase 1, was recorded at a concentration of 10 pM [41],... 

In addition. Das et ah demonstrated the effects of fucoxanthin on osteoclastogenesis. Treatment with 2.5 M fucoxanthin also induced apoptosis accompanied by activation of caspase-3 in osteoclast-like cells. Those in vitro studies suggest that fucoxanthin suppresses osteoclastogenesis via the inhibition of osteoclast differentiation and the induction of apoptosis in osteoclasts (Das et ah, 2010). Hence, dietary fucoxanthin may be useful for the prevention of bone diseases such as osteoporosis and rheumatoid arthritis, which are known to be related to bone resorption. 

An inhibitor of osteoclast differentiation and / or function is expected to be useful for treatment of bone lytic diseases such as osteoporosis, rheumatoid arthritis, and tumor metastasis into bone. Paenol inhibits RANKL-induced osteoclastogenesis by inhibiting ERK, p38, and NF-kB pathway (Tsai et ah, 2008). S)unbioimine (Fig. 32.2A) from the symbiotic marine dinoflagellate Symbiodinium sp. exhibits inhibitory effect on osteoclast differentiation (Kita et ah, 2004). 

Vallet, S.et al. (2007) MLN3897, a novel CCRl inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts. Blood, 10, 3744—3752. 

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