Al Saedi Ahmed, Stupka Nicole, Duque Gustavo
Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St. Albans, VIC, Australia.
Department of Medicine, Melbourne Medical School - Western Precinct, The University of Melbourne, St. Albans, VIC, Australia.
Handb Exp Pharmacol. 2020;262:353-367. doi: 10.1007/164_2020_358.
Osteoporosis is a condition where bone resorption exceeds bone formation leading to degeneration. With an aging population, the prevalence of osteoporosis is on the rise. Although advances in the field have made progress in targeting the mechanisms of the disease, the efficacy of current treatments remains limited and is complicated by unexpected side effects. Therefore, to overcome this treatment gap, new approaches are needed to identify and elucidate the cellular mechanisms mediating the pathogenesis of osteoporosis, which requires a strong understanding of bone biology. This chapter will focus on bone cells (osteoclasts, osteoblasts, and osteocytes) and their role in the bone turnover process in normal physiology and in pathology. With regard to osteoclast function, the regulators and underpinning signaling pathways leading to bone resorption will be discussed. Decreased osteoblastogenesis also contributes to bone deterioration with aging and osteoporosis; hence the factors and signaling pathways mediating osteoblast formation and function will be examined. Osteocytes are mature osteoblasts embedded in bone matrix and act as endocrine cells; their role in bone health and pathology will also be reviewed. In addition, this chapter will explore the emerging role of adipocytes in bone biology and the implications of increased bone marrow fat infiltration with aging on bone degeneration. In conclusion, a greater understanding of the pathogenesis of osteoporosis is of utmost importance in order to develop more effective treatments for osteoporosis and other bone diseases.
骨质疏松症是一种骨吸收超过骨形成导致骨质退变的病症。随着人口老龄化,骨质疏松症的患病率正在上升。尽管该领域的进展在针对疾病机制方面取得了进步,但目前治疗方法的疗效仍然有限,并且因意外的副作用而变得复杂。因此,为了克服这一治疗差距,需要新的方法来识别和阐明介导骨质疏松症发病机制的细胞机制,这需要对骨生物学有深入的了解。本章将重点介绍骨细胞(破骨细胞、成骨细胞和骨细胞)及其在正常生理和病理状态下骨转换过程中的作用。关于破骨细胞功能,将讨论导致骨吸收的调节因子和基础信号通路。成骨细胞生成减少也会导致随着年龄增长和骨质疏松症而出现的骨质恶化;因此,将研究介导成骨细胞形成和功能的因素及信号通路。骨细胞是嵌入骨基质中的成熟成骨细胞,并作为内分泌细胞发挥作用;它们在骨骼健康和病理中的作用也将得到综述。此外,本章将探讨脂肪细胞在骨生物学中的新作用,以及随着年龄增长骨髓脂肪浸润增加对骨质退变的影响。总之,为了开发更有效的骨质疏松症和其他骨疾病治疗方法,深入了解骨质疏松症的发病机制至关重要。