An adhesion G protein-coupled receptor is required in cartilaginous and dense connective tissues to maintain spine alignment.
An adhesion G protein-coupled receptor is required in cartilaginous and dense connective tissues to maintain spine alignment.
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DOI：
10.7554/elife.67781
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发表时间：
2021-07-28
期刊：
影响因子：
7.7
通讯作者：
Gray RS
中科院分区：
文献类型：
--
作者：
Liu Z;Hussien AA;Wang Y;Heckmann T;Gonzalez R;Karner CM;Snedeker JG;Gray RS
青少年特发性脊柱侧凸（adolescent idiopathic scoliosis，AIS）是世界范围内儿童最常见的脊柱疾病，但其发病机制尚不清楚。在这里，我们证明了中轴骨骼、椎间盘和致密结缔组织（即，韧带和肌腱）对于维持脊柱排列是必不可少的。我们表明，粘附G蛋白偶联受体ADGRG6，以前牵连在人类AIS协会的研究，是需要在这些组织中，以保持典型的脊柱排列在小鼠。此外，我们发现ADGRG6调节肌腱的生物力学特性，并刺激CREB信号传导，控制脊柱软骨组织中的基因表达。用cAMP激动剂治疗可以反映培养物中受体功能的方面，从而确定调节这些轴向软骨和结缔组织的核心途径。由于ADGRG6是人类AIS的关键基因，这些发现为人类脊柱侧凸开辟了新的治疗机会。
Adolescent idiopathic scoliosis (AIS) is the most common spine disorder affecting children worldwide, yet little is known about the pathogenesis of this disorder. Here, we demonstrate that genetic regulation of structural components of the axial skeleton, the intervertebral discs, and dense connective tissues (i.e., ligaments and tendons) is essential for the maintenance of spinal alignment. We show that the adhesion G protein-coupled receptor ADGRG6, previously implicated in human AIS association studies, is required in these tissues to maintain typical spine alignment in mice. Furthermore, we show that ADGRG6 regulates biomechanical properties of tendon and stimulates CREB signaling governing gene expression in cartilaginous tissues of the spine. Treatment with a cAMP agonist could mirror aspects of receptor function in culture, thus defining core pathways for regulating these axial cartilaginous and connective tissues. As ADGRG6 is a key gene involved in human AIS, these findings open up novel therapeutic opportunities for human scoliosis.