Connexins in the skeleton.
Connexins in the skeleton.
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DOI：
10.1016/j.semcdb.2015.12.017
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发表时间：
2016-02
影响因子：
7.3
通讯作者：
Civitelli R
中科院分区：
文献类型：
--
作者：
Stains JP;Civitelli R
骨骼的成型（建模）及其在整个生命过程中的维持（重塑）需要骨形成（成骨细胞）和再吸收细胞（破骨细胞）以及骨细胞（骨嵌入细胞）之间的协调活动。差距连接蛋白连接蛋白43（Cx43）已成为骨骼生长和稳态的关键调节剂。骨发育异常存在于眼齿指和颅骺发育不良，都与Cx43基因（GJA 1）突变，表明骨骼是Cx43作用的主要部位。通过对骨谱系细胞的直接作用，包括改变破骨细胞生成因子的产生，Cx43有助于获得峰值骨量、长骨的皮质建模和维持骨质量。Cx43还以多种方式促进骨对激素和机械信号的反应。骨骼生物学研究揭示了Cx43功能的复杂性;除了形成间隙连接和“半通道”外，Cx43还为信号分子提供了支架。因此，Cx43积极参与驱动骨骼发育和稳态的细胞信号的产生和调节。对Cx43的药理学干预可能在未来有助于补救因衰老、废用和激素失衡而发生的骨质恶化。
Shaping of the skeleton (modeling) and its maintenance throughout life (remodeling) require coordinated activity among bone forming (osteoblasts) and resorbing cells (osteoclasts) and osteocytes (bone embedded cells). The gap junction protein connexin43 (Cx43) has emerged as a key modulator of skeletal growth and homeostasis. The skeletal developmental abnormalities present in oculodentodigital and craniometaphyseal dysplasias, both linked to Cx43 gene (GJA1) mutations, demonstrate that the skeleton is a major site of Cx43 action. Via direct action on osteolineage cells, including altering production of pro-osteoclastogenic factors, Cx43 contributes to peak bone mass acquisition, cortical modeling of long bones, and maintenance of bone quality. Cx43 also contributes in diverse ways to bone responsiveness to hormonal and mechanical signals. Skeletal biology research has revealed the complexity of Cx43 function; in addition to forming gap junctions and “hemichannels”, Cx43 provides a scaffold for signaling molecules. Hence, Cx43 actively participates in generation and modulation of cellular signals driving skeletal development and homeostasis. Pharmacological interference with Cx43 may in the future help remedy deterioration of bone quality occurring with aging, disuse and hormonal imbalances.