Department of Orthopaedic Surgery, Center for Diabetes and Endocrine Research, University of Toledo, Toledo, OH, 43614, USA.
Harvard University, School of Dental Medicine, Boston, MA, 02115, USA.
Curr Osteoporos Rep. 2024 Jun;22(3):301-307. doi: 10.1007/s11914-024-00871-5. Epub 2024 Apr 16.
This review summarizes evidence on osteocyte support of extramedullary and bone marrow adipocyte development and discusses the role of endogenous osteocyte activities of nuclear receptors peroxisome proliferator-activated receptor gamma (PPARG) and alpha (PPARA) in this support.
PPARG and PPARA proteins, key regulators of glucose and fatty acid metabolism, are highly expressed in osteocytes. They play significant roles in the regulation of osteocyte secretome and osteocyte bioenergetics; both activities contributing to the levels of systemic energy metabolism in part through an effect on metabolic function of extramedullary and bone marrow adipocytes. The PPARs-controlled osteocyte endocrine/paracrine activities, including sclerostin expression, directly regulate adipocyte function, while the PPARs-controlled osteocyte fuel utilization and oxidative phosphorylation contribute to the skeletal demands for glucose and fatty acids, whose availability is under the control of adipocytes. Bone is an inherent element of systemic energy metabolism with PPAR nuclear receptors regulating osteocyte-adipocyte metabolic axes.
本文总结了破骨细胞对骨髓外和骨髓脂肪细胞发育的支持作用的证据,并讨论了核受体过氧化物酶体增殖物激活受体 γ (PPARG)和α (PPARA)的内源性破骨细胞活性在这种支持中的作用。
葡萄糖和脂肪酸代谢的关键调节因子 PPARG 和 PPARA 蛋白在破骨细胞中高度表达。它们在破骨细胞分泌组和破骨细胞生物能量学的调节中发挥重要作用;这两种活性部分通过对骨髓外和骨髓脂肪细胞的代谢功能的影响,有助于全身能量代谢水平。PPAR 调控的破骨细胞内分泌/旁分泌活性,包括骨钙素的表达,直接调节脂肪细胞功能,而 PPAR 调控的破骨细胞燃料利用和氧化磷酸化有助于骨骼对葡萄糖和脂肪酸的需求,而脂肪细胞控制着它们的可用性。骨骼是全身能量代谢的固有组成部分,核受体过氧化物酶体增殖物激活受体调节着破骨细胞-脂肪细胞代谢轴。