Osteoprotegerin decreases human osteoclast apoptosis by inhibiting the TRAIL pathway
Osteoprotegerin decreases human osteoclast apoptosis by inhibiting the TRAIL pathway
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DOI：
10.1002/jcp.21430
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发表时间：
2008-08-01
影响因子：
5.6
通讯作者：
Roux, Sophie
中科院分区：
文献类型：
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作者：
Chamoux, Estelle;Houde, Nicolas;Roux, Sophie
骨保护素（Osteoprotegerin， OPG）是一种分泌性诱饵受体，识别RANKL，阻断RANK和RANKL之间的相互作用，从而抑制破骨细胞的分化和活化。由于OPG是骨吸收的主要抑制剂，我们想知道OPG是否可以调节破骨细胞的存活/凋亡。通过将不同剂量的OPG添加到脐带血单核细胞的人破骨细胞培养物中来评估破骨细胞的凋亡。令人惊讶的是，加入OPG后细胞凋亡减少。我们推测OPG可能会阻断其参与破骨细胞凋亡的第二配体TRAIL。我们发现破骨细胞表达TRAIL，并且在OPG存在的情况下，培养基中的TRAIL水平呈剂量依赖性下降，破骨细胞中活化的caspase-8水平也是如此。此外，OPG的存在不影响破骨细胞TRAIL的表达。我们的研究结果表明，OPG至少在一定程度上通过结合并抑制人破骨细胞培养物中内源性产生的TRAIL来抑制破骨细胞凋亡。TRAIL可能是调节破骨细胞存活/凋亡的自分泌因子。
Osteoprotegerin (OPG) is a secreted decoy receptor that recognizes RANKL, and blocks the interaction between RANK and RANKL, leading to the inhibition of osteoclast differentiation and activation. As OPG is a major inhibitor of bone resorption, we wondered whether OPG could modulate osteoclast survival/apoptosis. Osteoclast apoptosis was evaluated by adding various doses of OPG to human osteoclast cultures obtained from cord blood monocytes. Surprisingly, apoptosis decreased after adding the OPG. We hypothesized that OPG may block its second ligand, TRAIL, which is involved in osteoclast apoptosis. We showed that osteoclasts expressed TRAIL, and that TRAIL levels in the culture medium dose-dependently decreased in presence of OPG, as did the level of activated caspase-8 in osteoclasts. In addition, the expression of TRAIL by osteoclasts was not affected in the presence of OPG. Our findings suggest that OPG inhibits osteoclast apoptosis, at least in part, by binding and thus inhibiting endogenously produced TRAIL in human osteoclast cultures. TRAIL could be an autocrine factor for the regulation of osteoclast survival/apoptosis.