Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.
Department of Pathology, Medical University of South Carolina, Charleston, South Carolina, USA.
J Mol Endocrinol. 2022 Aug 22;69(3):R109-R124. doi: 10.1530/JME-22-0076. Print 2022 Oct 1.
The aryl hydrocarbon receptor (AhR) has been implicated in regulating skeletal progenitor cells and the activity of bone-forming osteoblasts and bone-resorbing osteoclasts, thereby impacting bone mass and the risk of skeletal fractures. The AhR also plays an important role in the immune system within the skeletal niche and in the differentiation of mesenchymal stem cells into other cell lineages including chondrocytes and adipocytes. This transcription factor responds to environmental pollutants which can act as AhR ligands, initiating or interfering with various signaling cascades to mediate downstream effects, and also responds to endogenous ligands including tryptophan metabolites. This review comprehensively describes the reported roles of the AhR in skeletal cell biology, focusing on mesenchymal stem cells, osteoblasts, and osteoclasts, and discusses how AhR exhibits sexually dimorphic effects in bone. The molecular mechanisms mediating AhR's downstream effects are highlighted to emphasize the potential importance of targeting this signaling cascade in skeletal disorders.
芳香烃受体 (AhR) 已被牵涉到调节骨骼祖细胞以及成骨细胞（形成骨骼的细胞）和破骨细胞（分解骨骼的细胞）的活性，从而影响骨量和骨骼骨折的风险。AhR 还在骨骼龛位的免疫系统以及间充质干细胞向其他细胞谱系（包括软骨细胞和脂肪细胞）的分化中发挥重要作用。这种转录因子对环境污染物作出反应，这些污染物可以作为 AhR 配体，启动或干扰各种信号级联反应来介导下游效应，也对包括色氨酸代谢物在内的内源性配体作出反应。这篇综述全面描述了 AhR 在骨骼细胞生物学中的报告角色，重点关注间充质干细胞、成骨细胞和破骨细胞，并讨论了 AhR 在骨骼中表现出性别二态效应的方式。强调了介导 AhR 下游效应的分子机制，以强调靶向这一信号级联反应在骨骼疾病中的潜在重要性。
