An essential role for the association of CD47 to SHPS-1 in skeletal remodeling.
An essential role for the association of CD47 to SHPS-1 in skeletal remodeling.
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DOI：
10.1002/jbmr.441
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发表时间：
2011-09
影响因子：
6.2
通讯作者：
Clemmons, David R.
中科院分区：
文献类型：
--
作者：
Maile, Laura A.;DeMambro, Victoria E.;Wai, Christine;Aday, Ariel W.;Capps, Byron E.;Beamer, Wesley G.;Rosen, Clifford J.;Clemmons, David R.
整合素相关蛋白（IAP/CD47）参与巨噬细胞-巨噬细胞融合。为了了解CD47在骨骼重塑中的作用，我们比较了CD47−/−和CD47 +/+对照。与对照组相比，Cd47−/−小鼠体重更轻，面骨矿物质密度降低。Cd47−/−股骨长度较短，皮质较薄，由于小梁数量和厚度减少，小梁体积较小。组织形态测量显示骨形成和矿物质附着率减少，并伴有成骨细胞数量减少。Cd47 - / -小鼠的侵蚀面/骨表面减少了40%，但破骨细胞数量无显著差异。在体外，与野生型培养相比，分化Cd47 - / -骨髓细胞形成的功能性破骨细胞数量显著减少，并与骨吸收能力下降有关。此外，通过破坏CD47-SHPS-1的关联，我们发现破骨细胞的发生明显受损。对破骨细胞成熟标志物的检测表明，该缺陷位于融合点而非分化点，并且与缺乏SHPS-1磷酸化、SHP-1磷酸酶募集以及随后非肌肉细胞肌球蛋白IIA的去磷酸化有关。我们还证明了来自Cd47 - / -小鼠的骨髓基质细胞成骨发生的显著减少。我们发现Cd47 - / -成骨细胞和破骨细胞分化中的细胞自主缺陷，加上Cd47 - / -小鼠明显的骨骼表型，支持了Cd47通过其对骨形成和再吸收的作用在调节骨骼获得和维持中起重要作用的结论。
Integrin associated protein (IAP/CD47) has been implicated in macrophage-macrophage fusion. To understand the actions of CD47 on skeletal remodeling, we compared Cd47−/− with Cd47+/+ controls. Cd47−/− mice weighed less and had decreased areal bone mineral density compared to controls. Cd47−/− femurs were shorter in length with thinner cortices and exhibited lower trabecular bone volume due to decreased trabecular number and thickness. Histomorphometry revealed reduced bone formation and mineral apposition rates, accompanied by decreased osteoblast numbers. No differences in osteoclast number were observed despite a non-significant, but 40% decrease, in eroded surface/bone surface in Cd47−/− mice. In vitro the number of functional osteoclasts formed by differentiating Cd47−/− bone marrow cells was significantly decreased compared to wild-type cultures and was associated with a decrease in bone resorption capacity. Furthermore, by disrupting the CD47-SHPS-1 association we found that osteoclastogenesis was markedly impaired. Assays for markers of osteoclast maturation suggested the defect was at the point of fusion and not differentiation, and was associated with a lack of SHPS-1 phosphorylation, SHP-1 phosphatase recruitment and subsequent dephosphorylation of non-muscle cell myosin IIA. We also demonstrated a significant decrease in osteoblastogenesis in bone marrow stromal cells derived from Cd47−/− mice. Our finding of cell autonomous defects in Cd47−/− osteoblast and osteoclast differentiation coupled with the pronounced skeletal phenotype of Cd47−/− mice support the conclusion that CD47 plays an important role in regulating skeletal acquisition and maintenance through its actions on both bone formation and resorption.
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影响因子：
7.3
作者：
Rangaswami H;Schwappacher R;Marathe N;Zhuang S;Casteel DE;Haas B;Chen Y;Pfeifer A;Kato H;Shattil S;Boss GR;Pilz RB
通讯作者：
Pilz RB
影响因子：
6.2
作者：
Beamer, Wesley G.;Shultz, Kathryn L.;Rosen, Clifford J.
通讯作者：
Rosen, Clifford J.
影响因子：
4.8
作者：
McMichael, Brooke K.;Wysolmerski, Robert B.;Lee, Beth S.
通讯作者：
Lee, Beth S.
影响因子：
5.3
作者：
Saginario, C;Sterling, H;Vignery, A
通讯作者：
Vignery, A
影响因子：
4.8
作者：
Delahunty, K. M.;Shultz, K. L.;Rosen, C. J.
通讯作者：
Rosen, C. J.