Inhibition of terminal chondrocyte differentiation by bone morphogenetic protein 7 (OP-1) in vitro depends on the periarticular region but is independent of parathyroid hormone-related peptide
Inhibition of terminal chondrocyte differentiation by bone morphogenetic protein 7 (OP-1) in vitro depends on the periarticular region but is independent of parathyroid hormone-related peptide
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DOI：
10.1016/s8756-3282(99)00189-1
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发表时间：
1999-10-01
期刊：
影响因子：
4.1
通讯作者：
Burger, EH
中科院分区：
文献类型：
--
作者：
Haaijman, A;Karperien, M;Burger, EH
骨形态发生蛋白-7或BMP-7（OP-1）在胚胎长骨的软骨膜中高度表达，并且被认为在软骨内骨化中起作用。以前，我们已经表明，BMP-7抑制终端软骨细胞分化，也就是说，软骨细胞肥大和矿化培养外植体的胚胎小鼠跖骨。然而，这种抑制的机制和BMP-7的靶细胞仍然是未知的，在本研究中，我们表明BMP-7通过与外植体的关节周围区域的相互作用间接抑制终末软骨细胞分化，该区域也表达甲状旁腺相关肽（PTHrP），PTHrP通过抑制前肥大软骨细胞的肥大分化来调节终末软骨细胞分化，分化中心进而通过涉及印度刺猬（Ihh）的反馈回路调节PTHrP表达，印度刺猬（Ihh）在前肥大软骨细胞中表达。Ihh被认为作用于软骨膜细胞，软骨膜细胞进而开始表达刺激关节周围区域中PTHrP表达的迄今未知的介质。已经提出该因子属于BMP家族，我们研究了BMP-7对终末软骨细胞分化的抑制是否是由于PTHrP-Ihh反馈环的上调以及BMP-7是否是该环中的未知因子。我们发现，外源性BMF-7并没有上调培养的野生型胚胎跖骨中PTHrP、Ihh或PTH/PTHrP受体的mRNA表达。（PTHrP-/-）小鼠胚胎，这些数据表明，BMP-7介导的抑制终末软骨细胞分化在体外是独立的PTHrP-Ihh反馈回路。我们得出结论，BMP-7通过关节周围区域产生的未知抑制因子在体外调节胎儿骨外植体的终末软骨细胞分化和软骨矿化，（C）1999，Elsevier Science Inc. All rights reserved.
Bone morphogenetic protein-7, or BMP-7 (OP-l), is highly expressed in the perichondrium of embryonic long bones and is thought to play a role in endochondral ossification. Previously we have shown that BMP-7 inhibits terminal chondrocyte differentiation; that is, chondrocyte hypertrophy and mineralization in cultured explants of embryonic mouse metatarsals. However, the mechanism of this inhibition and the target cells of BMP-7 are still unknown, In this study we show that BMP-7 inhibits terminal chondrocyte differentiation indirectly, via an interaction with the periarticular region of the explants, This region also expresses parathyroid hormone-related peptide (PTHrP), PTHrP regulates terminal chondrocyte differentiation by inhibiting hypertrophic differentiation of prehypertrophic chondrocytes, The differentiating center in turn regulates PTHrP expression via a feedback loop involving Indian hedgehog (Ihh), which is expressed in the prehypertrophic chondrocytes, Ihh is thought to act on perichondrial cells, which in turn start to express an as yet unknown mediator that stimulates PTHrP expression in the periarticular region, It has been suggested that this factor belongs to the BMP-family, We investigated whether the inhibition of terminal chondrocyte differentiation by BMP-7 was due to upregulation of the PTHrP-Ihh feedback loop and whether BMP-7 was the unknown factor in the loop. Here we show that exogeneous BMF-7 did not upregulate the mRNA expression of PTHrP, Ihh, or the PTH/PTHrP receptor in cultured wild-type embryonic metatarsals, Furthermore, BMP-7 could still inhibit terminal chondrocyte differentiation in the metatarsals of PTHrP-deficient (PTHrP-/-) mouse embryos, These data indicate that the BMP-7-mediated inhibition of terminal chondrocyte differentiation in vitro is independent of the PTHrP-Ihh feedback loop. We concluded that BMP-7 modulates terminal chondrocyte differentiation and cartilage mineralization of fetal bone explants in vitro via as yet unknown inhibitory factor(s) produced in the periarticular region, (C) 1999 by Elsevier Science Inc. All rights reserved.