Kiryaman Gokce, Enabulele Irobosa, Banville Myra L, Divieti Pajevic Paola
Translational Dental Medicine, Henry M. Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA.
Endocrinology. 2025 Feb 27;166(4). doi: 10.1210/endocr/bqaf034.
Over the past decade, advancements in cell line development and genetic tools have led to a wealth of new insights into the effects of parathyroid hormone (PTH), particularly on osteocytes-cells deeply embedded within the bone's mineral matrix. These cells were once believed to be inactive bystanders, with little, if any, role in skeletal and mineral homeostasis. This concept of passive osteocytes has been challenged in recent years and osteocytes are now recognized for their crucial functions in skeletal mechanotransduction, bone modeling and remodeling, mineral ion regulation, and hematopoiesis. Moreover, osteocytes are key targets of PTH, and studies utilizing genetically modified mice, in which the PTH receptor is either deleted or overexpressed, have shed light on the hormone's complex effects on these cells. Several signaling molecules, including salt kinase inhibitors and histone deacetylases, have been identified as part of PTH's intracellular signaling cascade. In addition to its effects on bone metabolism, PTH has also been implicated in regulating bone energy metabolism, skeletal aging, and hematopoiesis. This review summarizes both classical and emerging effects of PTH on osteocytes, highlights the limitations of current research, and offers perspectives for future investigations in the field.
在过去十年中,细胞系开发和基因工具的进步使人们对甲状旁腺激素(PTH)的作用有了大量新的认识,特别是对深深嵌入骨矿物质基质中的骨细胞的作用。这些细胞曾被认为是无活性的旁观者,在骨骼和矿物质稳态中几乎没有作用。近年来,这种被动骨细胞的概念受到了挑战,现在人们认识到骨细胞在骨骼机械转导、骨建模和重塑、矿物质离子调节以及造血过程中起着至关重要的作用。此外,骨细胞是PTH的关键靶点,利用基因改造小鼠(其中PTH受体被删除或过表达)的研究揭示了该激素对这些细胞的复杂影响。几种信号分子,包括盐激酶抑制剂和组蛋白脱乙酰基酶,已被确定为PTH细胞内信号级联反应的一部分。除了对骨代谢的影响外,PTH还与调节骨能量代谢、骨骼衰老和造血有关。这篇综述总结了PTH对骨细胞的经典和新出现的影响,强调了当前研究的局限性,并为该领域的未来研究提供了展望。