Osteoblast and osteocyte-specific loss of Connexin43 results in delayed bone formation and healing during murine fracture healing.
Osteoblast and osteocyte-specific loss of Connexin43 results in delayed bone formation and healing during murine fracture healing.
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DOI：
10.1002/jor.22178
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发表时间：
2013-01
影响因子：
2.8
通讯作者：
Donahue, Henry J.
中科院分区：
文献类型：
--
作者：
Loiselle, Alayna E.;Paul, Emmanuel M.;Lewis, Gregory S.;Donahue, Henry J.
缝隙连接蛋白43（Cx43）在体外成骨细胞分化和体内骨形成中起重要作用。成骨细胞/骨细胞特异性Cx43缺失的小鼠显示细胞间缝隙连接通讯（GJIC）、骨密度和皮质厚度降低。为了确定Cx43在骨折愈合中的作用，在骨钙素-Cre +; Cx43 flox/flox（Cx43 cKO）和Cre-Cx43 flox/flox（WT）小鼠中诱导闭合性股骨骨折。我们检验了Cx43缺失导致骨折后骨形成减少和愈合受损的假设。在这里，我们表明，成骨细胞和骨细胞特异性Cx43缺失导致骨折愈合过程中骨形成，骨重建和机械性能下降。Cx43 cKO小鼠显示骨体积、总体积减少，TRAP+破骨细胞减少。此外，与WT小鼠相比，成熟成骨细胞和骨细胞中Cx43的缺失导致骨折后21至35天之间的扭转刚度显著降低。这些研究确定了差距连接蛋白Cx43在骨折愈合过程中的新作用，表明Cx43的缺失可导致骨形成减少和骨吸收。因此，增强Cx43表达或GJIC可能提供一种新的手段，以促进骨折愈合过程中的骨形成。
Connexin43 (Cx43) plays an important role in osteoblastic differentiation in vitro, and bone formation in vivo. Mice with osteoblast/osteocyte specific loss of Cx43 display decreased gap junctional intercellular communication (GJIC), bone density and cortical thickness. To determine the role of Cx43 in fracture healing, a closed femur fracture was induced in Osteocalcin-Cre+; Cx43flox/flox (Cx43cKO) and Cre-Cx43flox/flox (WT) mice. We tested the hypothesis that loss of Cx43 results in decreased bone formation and impaired healing following fracture. Here we show that osteoblast and osteocyte-specific deletion of Cx43 results in decreased bone formation, bone remodeling, and mechanical properties during fracture healing. Cx43cKO mice display decreased bone volume, total volume, and fewer TRAP+ osteoclasts. Furthermore, loss of Cx43 in mature osteoblasts and osteocytes results in a significant decrease in torsional rigidity between 21 and 35 days post-fracture, compared to WT mice. These studies identify a novel role for the gap junction protein Cx43 during fracture healing, suggesting that loss of Cx43 can result in both decreased bone formation, and bone resorption. Therefore, enhancing Cx43 expression or GJIC may provide a novel means to enhance bone formation during fracture healing.
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DOI：
10.1016/s0006-291x(03)00502-3
发表时间：
2003-04-18
影响因子：
3.1
作者：
Ransjö, M;Sahli, J;Lie, A
通讯作者：
Lie, A
影响因子：
4.8
作者：
Plotkin, LI;Manolagas, SC;Bellido, T
通讯作者：
Bellido, T
影响因子：
3.3
作者：
Lecanda, F;Towler, DA;Civitelli, R
通讯作者：
Civitelli, R
DOI：
10.1152/ajpcell.2001.281.6.c1917
发表时间：
2001-12-01
影响因子：
5.5
作者：
Saunders, MM;You, J;Jacobs, CR
通讯作者：
Jacobs, CR
影响因子：
6.2
作者：
Bivi, Nicoletta;Condon, Keith W.;Allen, Matthew R.;Farlow, Nathan;Passeri, Giovanni;Brun, Lucas R.;Rhee, Yumie;Bellido, Teresita;Plotkin, Lilian I.
通讯作者：
Plotkin, Lilian I.