F-spondin deficient mice have a high bone mass phenotype.
F-spondin deficient mice have a high bone mass phenotype.
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DOI：
10.1371/journal.pone.0098388
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Abramson SB
中科院分区：
文献类型：
--
作者：
Palmer GD;Attur MG;Yang Q;Liu J;Moon P;Beier F;Abramson SB
F-spondin是一种细胞周围基质蛋白，在骨关节炎期间生长板软骨和关节软骨的发育中表达上调。为了研究其在体内骨和软骨中的功能，我们培养了缺乏F-spondin基因Spon1的小鼠。Spon1−/−小鼠存活并正常发育至成年，无重大骨骼异常。在6个月时，组织学染色和显微CT分析证明，Spon1 - / -小鼠的股骨和胫骨骨量增加，这种情况持续了12个月。相比之下，各年龄组的关节软骨均未见明显异常。免疫组化染色显示，Spon1−/−小鼠生长板区骨膜蛋白、碱性磷酸盐和酒石酸抗性酸性磷酸酶（TRAP）活性升高，表明骨合成和转换升高。然而，在不同基因型之间，TRAP、骨吸收标志物、CTX-1或破骨细胞分化潜能的血清水平没有差异。与野生型相比，敲除小鼠血清和培养的肋软骨细胞中TGF-β1的水平也有所降低。这伴随着胫骨和软骨细胞中bmp调节的smad， P-SMAD1/5水平的增加。我们的研究结果表明，Spon1作为骨量的负调节因子的作用以前未被认识到。我们推测Spon1缺失导致局部和全身TGF-β水平降低，从而导致成年小鼠BMP信号传导增加和骨沉积增加。
F-spondin is a pericellular matrix protein upregulated in developing growth plate cartilage and articular cartilage during osteoarthritis. To address its function in bone and cartilage in vivo, we generated mice that were deficient for the F-spondin gene, Spon1. Spon1 − /− mice were viable and developed normally to adulthood with no major skeletal abnormalities. At 6 months, femurs and tibiae of Spon1 − /− mice exhibited increased bone mass, evidenced by histological staining and micro CT analyses, which persisted up to 12 months. In contrast, no major abnormalities were observed in articular cartilage at any age group. Immunohistochemical staining of femurs and tibiae revealed increased levels of periostin, alkaline phosphate and tartrate resistant acid phosphatase (TRAP) activity in the growth plate region of Spon1 − /− mice, suggesting elevated bone synthesis and turnover. However, there were no differences in serum levels of TRAP, the bone resorption marker, CTX-1, or osteoclast differentiation potential between genotypes. Knockout mice also exhibited reduced levels of TGF-β1 in serum and cultured costal chondrocytes relative to wild type. This was accompanied by increased levels of the BMP-regulatory SMADs, P-SMAD1/5 in tibiae and chondrocytes. Our findings indicate a previously unrecognized role for Spon1 as a negative regulator of bone mass. We speculate that Spon1 deletion leads to a local and systemic reduction of TGF-β levels resulting in increased BMP signaling and increased bone deposition in adult mice.
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影响因子：
4.1
作者：
Delany AM;Hankenson KD
通讯作者：
Hankenson KD
影响因子：
3.5
作者：
Peterziel, H.;Sackmann, T.;Unsicker, K.
通讯作者：
Unsicker, K.
影响因子：
4.8
作者：
Javed, Amjad;Bae, Jong-Sup;Lian, Jane B.
通讯作者：
Lian, Jane B.
DOI：
10.1083/jcb.201003089
发表时间：
2010-09-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nistala H;Lee-Arteaga S;Smaldone S;Siciliano G;Carta L;Ono RN;Sengle G;Arteaga-Solis E;Levasseur R;Ducy P;Sakai LY;Karsenty G;Ramirez F
通讯作者：
Ramirez F
影响因子：
64.5
作者：
KLAR, A;BALDASSARE, M;JESSELL, TM
通讯作者：
JESSELL, TM