Westendorf Jennifer J
Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Cell Biochem. 2007 Oct 1;102(2):332-40. doi: 10.1002/jcb.21486.
Skeletogenesis occurs continuously during the lifespan of vertebrate organisms. In development, the skeleton is patterned and modeled until each bone achieves its optimal shape and full size. During adults, the skeleton is remodeled to maintain strength and release calcium. The bone-resorbing and bone-forming activities of osteoclasts and osteoblasts, respectively, are tightly coupled to maintain optimal skeletal health; however, during aging and disease, these cells can become uncoupled, adversely affecting skeletal health and strength. Histone deacetylases have emerged as important regulators of endochondral bone formation, osteoblast maturation and osteoclast survival. Histone deacetylases are inhibited by small molecules that are approved and/or in clinical trials as cancer therapeutic drugs or anti-epileptic agents. In this article, the roles of histone deacetylases and effects of histone deacetylase inhibitors on bone and cartilage cells are reviewed.
骨骼生成在脊椎动物的生命周期中持续发生。在发育过程中,骨骼形成图案并塑形,直到每块骨头达到其最佳形状和完整大小。在成年期,骨骼会进行重塑以维持强度并释放钙。破骨细胞和成骨细胞的骨吸收和骨形成活动分别紧密耦合,以维持最佳的骨骼健康;然而,在衰老和疾病过程中,这些细胞可能会解耦,对骨骼健康和强度产生不利影响。组蛋白脱乙酰酶已成为软骨内骨形成、成骨细胞成熟和破骨细胞存活的重要调节因子。组蛋白脱乙酰酶受到小分子的抑制,这些小分子已被批准作为癌症治疗药物或抗癫痫药物和/或正在进行临床试验。在本文中,我们综述了组蛋白脱乙酰酶的作用以及组蛋白脱乙酰酶抑制剂对骨和软骨细胞的影响。