Bone: Osteocyte RANKL in bone homeostasis: a paradigm shift?
Bone: Osteocyte RANKL in bone homeostasis: a paradigm shift?
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DOI：
10.1038/nrrheum.2011.151
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发表时间：
2011-10-11
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影响因子：
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通讯作者：
Killock, David
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作者：
Killock, David
但显示从这些小鼠中纯化的骨细胞与对照同窝出生的小鼠相比，在体外支持破骨细胞生成的能力降低。有趣的是，Takayanagi等人发现出生时Dmp 1-RANKL科斯中的破骨细胞数量正常，而两组出生后与对照组相比，破骨细胞数量减少> 70%。奥布莱恩说：“嵌在骨基质中的细胞控制破骨细胞的形成，这是一个很大的惊喜。”两个研究小组继续研究骨细胞在骨稳态中的作用。他们的综合数据表明，与对照组相比，Dmp 1-RANKL KO与出生后骨矿物质密度（BMD）和体积的增加以及骨髓腔的骨填充相关。此外，Dmp 1-RANKL KO小鼠的骨形成和骨吸收标志物均降低。这些数据表明，出生后，“骨细胞是RANKL的主要来源，因此调节破骨细胞的形成和骨吸收，”Takayanagi说。奥布莱恩等人还使用卸载诱导的骨丢失模型证明了骨细胞RANKL在病理性骨重建中的作用;对照小鼠骨中RANKL mRNA和破骨细胞数量的增加与BMD、小梁间距和皮质厚度的变化相关，但在Dmp 1-RANKL科斯中未观察到。这些发现是“…与先前存在的RANKL由成骨细胞或骨髓基质细胞表达的教条相反，但与骨细胞是调节其他骨细胞的机械感受细胞的概念一致，”Takayanagi说。“我们论文中提出的概念挑战了一个长期存在的模式."，奥布莱恩补充说。“现在重要的是确定骨细胞产生的RANKL是否在导致病理性骨丢失的情况下很重要，例如性类固醇丢失，衰老或炎症，”他继续说道。
but showed that osteocytes purified from these mice had reduced ability to support osteoclastogenesis in vitro, compared with those from control littermates. Interestingly, Takayanagi et al. found normal osteoclast numbers in Dmp1–RANKL KOs at birth, whereas both groups found a> 70% reduction postnatally compared with controls.“It was a big surprise that cells embedded within the bone matrix control osteoclast formation,” claims O’Brien. Both research groups went on to examine the role of osteocytes in bone homeostasis. Their combined data demonstrated that Dmp1–RANKL KO was associated with postnatal increases in bone mineral density (BMD) and volume compared with controls, and filling of the bone marrow cavity with bone. Additionally, markers of both bone formation and resorption were decreased in Dmp1–RANKL KO mice. These data suggest that, postnatally,“osteocytes are the major source of RANKL and thus regulate osteoclast formation and bone resorption,” says Takayanagi. O’Brien et al. also demonstrated a role for osteocyte RANKL in pathological bone remodeling using a model of unloading-induced bone loss; increases in RANKL mRNA and osteoclast numbers in bones of control mice were associated with changes in BMD, trabecular spacing and cortical thickness, but were not observed in Dmp1–RANKL KOs. These findings are “... contrary to the preexisting dogma that RANKL is expressed by osteoblasts or bone marrow stromal cells, but consistent with the concept that osteocytes are mechanosensing cells that regulate other bone cells,” states Takayanagi.“The concept put forward in our papers challenges a long-standing model...”, adds O’Brien.“Now it will be important to determine whether RANKL produced by osteocytes is important in situations that lead to pathological bone loss, such as loss of sex steroids, aging, or inflammation,” he continues.