Epiphyseal chondrocyte secondary ossification centers require thyroid hormone activation of Indian hedgehog and osterix signaling.
Epiphyseal chondrocyte secondary ossification centers require thyroid hormone activation of Indian hedgehog and osterix signaling.
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DOI：
10.1002/jbmr.2256
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发表时间：
2014-10
影响因子：
6.2
通讯作者：
Mohan, Subburaman
中科院分区：
文献类型：
--
作者：
Xing, Weirong;Cheng, Shaohong;Wergedal, Jon;Mohan, Subburaman
已知甲状腺激素（TH）通过直接作用于软骨细胞和成骨细胞来调节骨骼发育过程中的软骨内骨化。在这项研究中，我们专注于TH对次级骨化中心（SOC）的影响，因为在几个物种中SOC的出现时间与TH达到峰值水平的时间一致。因此，TH缺陷小鼠和对照小鼠第21天股骨和胫骨的μCT评价显示，由于TH缺陷，SOC的软骨内骨化严重受损，TH治疗10天完全挽救了这种表型。骨骺中软骨和骨的染色显示，虽然在青春期前对照小鼠中所有的软骨都转化为骨，但这种转化在TH缺陷小鼠中没有发生。免疫组织化学研究显示，TH处理Tshr−/−小鼠诱导第7天SOC中表达Col 2的软骨细胞表达Ihh和Osx，随后在第10天分化为表达Col 10/骨钙素的软骨成骨细胞。与这些数据一致，用10 ng/ml TH处理来自3日龄小鼠的胫骨培养物使骨骺中Osx、Col 10、ALP和骨钙素的表达增加6-60倍。此外，敲低TH诱导的Osx表达的增加，使用慢病毒shRNA显着阻断TH诱导的ALP和骨钙素在软骨细胞中的表达。用Ihh抑制剂处理软骨形成细胞可消除软骨成骨细胞分化和SOC形成。我们的研究结果表明，TH通过刺激软骨细胞中Ihh和Osx的表达，将软骨细胞分化为产生骨基质的成骨细胞，从而调节SOC的起始和进展。
Thyroid hormones (TH) are known to regulate endochondral ossification during skeletal development via acting directly in chondrocytes and osteoblasts. In this study, we focused on TH effects on the secondary ossification center (SOC), since the time of appearance of SOCs in several species coincides with the time when peak levels of TH are attained. Accordingly, μCT evaluation of femurs and tibias at day 21 in TH-deficient and control mice revealed that endochondral ossification of SOCs is severely compromised due to TH deficiency and that TH treatment for 10 days completely rescued this phenotype. Staining of cartilage and bone in the epiphysis revealed that while all of the cartilage is converted into bone in the prepubertal control mice, this conversion failed to occur in the TH-deficient mice. Immunohistochemistry studies revealed that TH treatment of Tshr−/− mice induced expression of Ihh and Osx in Col2 expressing chondrocytes in the SOC at day 7 which subsequently differentiate into Col10/osteocalcin expressing chondro-osteoblasts at day 10. Consistent with these data, treatment of tibia cultures from 3-day old mice with10 ng/ml TH increased expression of Osx, Col10, ALP and osteocalcin in the epiphysis by 6–60 fold. Furthermore, knockdown of the TH-induced increase in Osx expression using lentiviral shRNA significantly blocked TH-induced ALP and osteocalcin expression in chondrocytes. Treatment of chondrogenic cells with an Ihh inhibitor abolished chondro-osteoblast differentiation and SOC formation. Our findings indicate that TH regulates the SOC initiation and progression via differentiating chondrocytes into bone matrix producing osteoblasts by stimulating Ihh and Osx expression in chondrocytes.
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影响因子：
158.5
作者：
Bochukova, Elena;Schoenmakers, Nadia;Chatterjee, Krishna
通讯作者：
Chatterjee, Krishna
影响因子：
--
作者：
Bassett, J. H. Duncan;O'Shea, Patrick J.;Williams, Graham R.
通讯作者：
Williams, Graham R.
影响因子：
4.1
作者：
Beamer, WG;Donahue, LR;Baylink, DJ
通讯作者：
Baylink, DJ
DOI：
10.1002/jbmr.1639
发表时间：
2012-08
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Dao DY;Jonason JH;Zhang Y;Hsu W;Chen D;Hilton MJ;O'Keefe RJ
通讯作者：
O'Keefe RJ
影响因子：
7.8
作者：
CANCEDDA, FD;GENTILI, C;CANCEDDA, R
通讯作者：
CANCEDDA, R