Stanniocalcin 1 acts as a paracrine regulator of growth plate chondrogenesis
Stanniocalcin 1 acts as a paracrine regulator of growth plate chondrogenesis
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DOI：
10.1074/jbc.m506667200
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发表时间：
2006-02-24
影响因子：
4.8
通讯作者：
De Luca, F
中科院分区：
文献类型：
--
作者：
Wu, SF;Yoshiko, Y;De Luca, F
在胚胎发育过程中，哺乳动物斯钙素（STC 1）的表达在approximular骨骼表明其参与纵向骨生长的调节。过表达STC 1的小鼠中存在侏儒症进一步支持了这种作用。然而，STC 1对生长的抑制作用可能与出生后代谢异常和出生前骨形成缺陷有关。在我们的研究中，我们使用器官培养系统来评估STC对生长板软骨形成的影响，这是纵向骨生长的主要决定因素。在重组人STC（rhSTC）存在下培养胎鼠跖骨。3天后，rhSTC抑制跖骨生长、生长板软骨细胞增殖和肥大/分化以及细胞外基质合成。此外，rhSTC增加生长板中凋亡软骨细胞的数量。在培养的软骨细胞中，rhSTC增加磷酸盐摄取，减少软骨细胞增殖和基质合成，并诱导凋亡。所有这些作用都被逆转培养软骨细胞与rhSTC和膦甲酸，磷酸盐转运的抑制剂。rhSTC介导的抑制跖骨生长和生长板软骨细胞的增殖和肥大/分化被废除与rhSTC和膦甲酸培养跖骨。总之，我们的研究结果表明，STC 1抑制纵向骨生长直接在生长板。这种生长抑制可能由软骨细胞磷酸盐摄取增加介导，由软骨细胞增殖、肥大/分化和基质合成受抑制以及细胞凋亡增加引起。最后，STC 1及其结合位点在生长板中的表达将支持该生长因子在生长板软骨形成的调节中的自分泌/旁分泌作用。
During embryogenesis, the expression of mammalian stanniocalcin (STC1) in the appendicular skeleton suggests its involvement in the regulation of longitudinal bone growth. Such a role is further supported by the presence of dwarfism in mice overexpressing STC1. Yet, the STC 1 inhibitory effect on growth may be related to both postnatal metabolic abnormalities and prenatal defective bone formation. In our study, we used an organ culture system to evaluate the effects of STC on growth plate chondrogenesis, which is the primary determinant of longitudinal bone growth. Fetal rat metatarsal bones were cultured in the presence of recombinant human STC (rhSTC). After 3 days, rhSTC suppressed metatarsal growth, growth plate chondrocyte proliferation and hypertrophy/differentiation, and extracellular matrix synthesis. In addition, rhSTC increased the number of apoptotic chondrocytes in the growth plate. In cultured chondrocytes, rhSTC increased phosphate uptake, reduced chondrocyte proliferation and matrix synthesis, and induced apoptosis. All these effects were reversed by culturing chondrocytes with rhSTC and phosphonoformic acid, an inhibitor of phosphate transport. The rhSTC-mediated inhibition of metatarsal growth and growth plate chondrocyte proliferation and hypertrophy/differentiation was abolished by culturing metatarsals with rhSTC and phosphonoformic acid. Taken together, our findings indicate that STC1 inhibits longitudinal bone growth directly at the growth plate. Such growth inhibition, likely mediated by an increased chondrocyte phosphate uptake, results from suppressed chondrocyte proliferation, hypertrophy/differentiation, and matrix synthesis and by increased apoptosis. Last, the expression of both STC1 and its binding site in the growth plate would support an autocrine/paracrine role for this growth factor in the regulation of growth plate chondrogenesis.