The perichondrium plays an important role in mediating the effects of TGF-β1 on endochondral bone formation
The perichondrium plays an important role in mediating the effects of TGF-β1 on endochondral bone formation
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DOI：
10.1002/dvdy.1141
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发表时间：
2001-07-01
影响因子：
2.5
通讯作者：
Serra, R
中科院分区：
文献类型：
--
作者：
Alvarez, J;Horton, J;Serra, R
软骨内骨形成是复杂的，需要多种因子和多种细胞类型的信号协调。因此，软骨细胞分化受软骨细胞和软骨膜细胞合成的因子调节。先前我们发现，在软骨膜/骨膜中表达转化生长因子β（TGF -β）Ⅱ型受体的显性负性形式会导致生长板软骨细胞肥大分化增加，这表明TGF -β向软骨膜发出的信号在体内限制终末分化中起作用。后来利用器官培养模型，我们证明TGF -β1通过两种不同机制抑制软骨细胞增殖和肥大分化。肥大分化的抑制被证明依赖于甲状旁腺激素相关肽（PTHrP），并且在用TGF -β1处理后软骨膜中PTHrP mRNA的表达受到刺激。在本报告中，对软骨膜是TGF -β1对小鼠跖骨器官培养中生长和/或肥大分化作用所必需的这一假设进行了检验。在软骨膜完整的跖骨培养中，TGF -β1处理抑制了X型胶原mRNA的表达。相反，在无软骨膜的培养中，通过X型胶原表达衡量的肥大分化不受TGF -β1抑制。添加到完整培养物中的TGF -β1抑制软骨细胞中BrdU的掺入，并增加软骨膜中的掺入；然而，TGF -β1处理刺激了经酶法去除软骨膜的跖骨中的软骨细胞增殖。这些结果表明，TGF -β1介导的对软骨细胞增殖和肥大分化的调节依赖于软骨膜。因此，软骨膜中的一种或多种因子可能介导软骨细胞对TGF -β1的反应。（C）2001威利 - 利斯公司
Endochondral bone formation is complex and requires the coordination of signals from several factors and multiple cell types. Thus, chondrocyte differentiation is regulated by factors synthesized by both chondrocytes and cells in the perichondrium, Previously, we showed that expression of a dominant-negative form of the transforming growth factor beta (TGF-beta) type II receptor in perichondrium/periosteum resulted in increased hypertrophic differentiation in growth plate chondrocytes, suggesting a role for TGF-beta signaling to the perichondrium in limiting terminal differentiation in vivo. Using an organ culture model, we later demonstrated that TGF-beta1 inhibits chondrocyte proliferation and hypertrophic differentiation by two separate mechanisms. Inhibition of hypertrophic differentiation was shown to be dependent on Parathyroid hormone-related peptide (PTHrP) and expression of PTHrP mRNA was stimulated in the perichondrium after treatment with TGF-beta1. In this report, the hypothesis that the perichondrium is required for the effects of TGF-beta1 on growth and/or hypertrophic differentiation in mouse metatarsal organ cultures is tested, Treatment with TGF-beta1 inhibited expression of type X collagen mRNA in metatarsal cultures with the perichondrium intact. In contrast, hypertrophic differentiation as measured by expression of Type X collagen was not inhibited by TGF-beta1 in perichondrium-free cultures. TGF-beta1 added to intact cultures inhibited BrdU incorporation in chondrocytes and increased incorporation in the perichondrium; however, TGF-beta1 treatment stimulated chondrocyte proliferation in metatarsals from which the perichondrium had been enzymatically removed. These results suggest that the TGF-beta1-mediated regulation of both chondrocyte proliferation and hypertrophic differentiation is dependent upon the perichondrium, Thus, one or several factors from the perichondrium might mediate the way chondrocytes respond to TGF-beta1. (C) 2001 Wiley-Liss, Inc.