Accelerated Cartilage Resorption by Chondroclasts during Bone Fracture Healing in Osteoprotegerin-Deficient Mice
Accelerated Cartilage Resorption by Chondroclasts during Bone Fracture Healing in Osteoprotegerin-Deficient Mice
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DOI：
10.1210/en.2009-0452
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发表时间：
2009-11-01
期刊：
影响因子：
4.8
通讯作者：
Toyama, Yoshiaki
中科院分区：
文献类型：
--
作者：
Ota, Norikazu;Takaishi, Hironari;Toyama, Yoshiaki
核因子κ B配体受体激活剂（RANKL）和骨保护素（OPG）是RANKL的诱饵受体，通过调节破骨细胞（骨吸收细胞）的分化来维持骨量。软骨内骨化和骨折愈合涉及软骨吸收，这是一个鲜为人知的过程，需要用骨代替软骨。在这里，我们描述了软骨细胞产生的OPG在破软骨细胞发生中的作用。与野生型小鼠相比，OPG（-/-）小鼠骨折愈合表现为骨折骨愈合更快，软骨愈伤组织吸收更快，软骨骨连接处的破软骨细胞数量增加。当将培养的OPG（-/-）软骨细胞小球移植到肾包膜下时，该小球募集了许多破软骨细胞。该颗粒在体外诱导RAW 264.7细胞产生抗酒石酸盐酸性磷酸酶阳性的多核细胞。最后，与脾脏细胞一起培养的OPG（-/-）软骨细胞（而不是野生型软骨细胞）诱导了许多抗酒石酸盐酸性磷酸酶阳性的多核细胞。软骨细胞中RANKL和OPG的表达受多种成骨因子的调控，包括1,25-二羟基维生素D-3、PTHrP、IL-1 α和tnf - β。因此，软骨细胞产生的局部OPG可能控制软骨吸收，作为软骨细胞依赖性破软骨细胞发生的负调节因子。（内分泌学150:4823-4834,2009）
Receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG), a decoy receptor of RANKL, maintain bone mass by regulating the differentiation of osteoclasts, which are bone-resorbing cells. Endochondral bone ossification and bone fracture healing involve cartilage resorption, a less well-understood process that is needed for replacement of cartilage by bone. Here we describe the role of OPG produced by chondrocytes in chondroclastogenesis. Fracture healing in OPG(-/-) mice showed faster union of the fractured bone, faster resorption of the cartilaginous callus, and an increased number of chondroclasts at the chondroosseous junctions compared with that in wild-type littermates. When a cultured pellet of OPG(-/-) chondrocytes was transplanted beneath the kidney capsule, the pellet recruited many chondroclasts. The pellet showed the ability to induce tartrate-resistant acid phosphatase-positive multinucleated cells from RAW 264.7 cells in vitro. Finally, OPG(-/-) chondrocytes (but not wild-type chondrocytes) cultured with spleen cells induced many tartrate-resistant acid phosphatase-positive multinucleated cells. The expression of RANKL and OPG in chondrocytes was regulated by several osteotropic factors including 1,25-dihydroxyvitamin D-3, PTHrP, IL-1 alpha, and TNF-beta. Thus, local OPG produced by chondrocytes probably controls cartilage resorption as a negative regulator for chondrocyte-dependent chondroclastogenesis. (Endocrinology 150: 4823-4834, 2009)