Osteolectin increases bone elongation and body length by promoting growth plate chondrocyte proliferation.
Osteolectin increases bone elongation and body length by promoting growth plate chondrocyte proliferation.
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Osteolectin通过促进生长板软骨细胞的增殖来增加骨骼伸长和身体长度。
DOI：
10.1073/pnas.2220159120
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发表时间：
2023-05-30
影响因子：
11.1
通讯作者：
Mariani, Francesca V.
中科院分区：
文献类型：
--
作者：
Zhang, Jingzhu;Du, Liming;Davis, Bethany;Gu, Zhimin;Lyu, Junhua;Zhao, Zhiyu;Xu, Jian;Morrison, Sean J.;Mariani, Francesca V.
Osteolectin promotes the maintenance of bone mass in adult mice, but there has not been genetic evidence that Osteolectin is functionally important in humans. In the current study, we identified a function for Osteolectin in juvenile mice: the promotion of bone elongation by increasing growth plate chondrocyte proliferation, leading to increased body length. Second, we describe a human genetic variant that suggests Osteolectin also promotes bone elongation in humans. The single-nucleotide variant (rs182722517) that is associated with reduced height and plasma Osteolectin levels in humans is also associated with reduced Osteolectin expression in bone marrow stromal cells. Osteolectin is a recently identified osteogenic growth factor that binds to Integrin α11 (encoded by Itga11), promoting Wnt pathway activation and osteogenic differentiation by bone marrow stromal cells. While Osteolectin and Itga11 are not required for the formation of the skeleton during fetal development, they are required for the maintenance of adult bone mass. Genome-wide association studies in humans reported a single-nucleotide variant (rs182722517) 16 kb downstream of Osteolectin associated with reduced height and plasma Osteolectin levels. In this study, we tested whether Osteolectin promotes bone elongation and found that Osteolectin-deficient mice have shorter bones than those of sex-matched littermate controls. Integrin α11 deficiency in limb mesenchymal progenitors or chondrocytes reduced growth plate chondrocyte proliferation and bone elongation. Recombinant Osteolectin injections increased femur length in juvenile mice. Human bone marrow stromal cells edited to contain the rs182722517 variant produced less Osteolectin and underwent less osteogenic differentiation than that of control cells. These studies identify Osteolectin/Integrin α11 as a regulator of bone elongation and body length in mice and humans.
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影响因子：
64.5
作者：
Liu X;Zhang Y;Chen Y;Li M;Zhou F;Li K;Cao H;Ni M;Liu Y;Gu Z;Dickerson KE;Xie S;Hon GC;Xuan Z;Zhang MQ;Shao Z;Xu J
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DOI：
10.1007/978-1-0716-1119-7_4
发表时间：
2021
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
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作者：
通讯作者：
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影响因子：
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作者：
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通讯作者：
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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：
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作者：
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