Jin Zixue, Li Xiaoxiao, Wan Yihong
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
Mol Endocrinol. 2015 Feb;29(2):172-86. doi: 10.1210/me.2014-1316. Epub 2014 Dec 30.
Osteoclasts are bone-resorbing cells essential for skeletal remodeling and regeneration. However, excessive osteoclasts often contribute to prevalent bone degenerative diseases such as osteoporosis, arthritis, and cancer bone metastasis. Osteoclast dysregulation is also associated with rare disorders such as osteopetrosis, pycnodysostosis, Paget's disease, and Gorham-Stout syndrome. The nuclear receptor (NR) family of transcription factors functions as metabolic sensors that control a variety of physiological processes including skeletal homeostasis and serves as attractive therapeutic targets for many diseases. In this review, we highlight recent findings on the new players and the new mechanisms for how NRs regulate osteoclast differentiation and bone resorption. An enhanced understanding of NR functions in osteoclastogenesis will facilitate the development of not only novel osteoprotective medicine but also prudent strategies to minimize the adverse skeletal effects of certain NR-targeting drugs for a better treatment of cancer and metabolic diseases.
破骨细胞是骨骼重塑和再生所必需的骨吸收细胞。然而,过多的破骨细胞常常导致诸如骨质疏松症、关节炎和癌症骨转移等常见的骨退行性疾病。破骨细胞功能失调还与诸如骨质石化症、致密性骨发育不全、佩吉特病和戈勒姆-斯托特综合征等罕见疾病有关。核受体(NR)转录因子家族作为代谢传感器,控制包括骨骼稳态在内的各种生理过程,并成为许多疾病有吸引力的治疗靶点。在本综述中,我们重点介绍了关于NRs如何调节破骨细胞分化和骨吸收的新参与者和新机制的最新发现。深入了解NRs在破骨细胞生成中的功能不仅将促进新型骨保护药物的开发,还将有助于制定谨慎的策略,以尽量减少某些靶向NRs药物对骨骼的不良影响,从而更好地治疗癌症和代谢性疾病。