Phenotypic research on senile osteoporosis caused by SIRT6 deficiency

作     者：De-Mao Zhang Di-Xin Cui Ruo-Shi Xu Ya-Chuan Zhou Li-Wei Zheng Peng Liu Xue-Dong Zhou 

作者机构：State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University 

出 版 物：《International Journal of Oral Science》 (国际口腔科学杂志（英文版）)

年 卷 期：2016年第8卷第2期

页      面：84-92页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by NSFC grants 81371136 and JCPT2011-9 (Xue-Dong Zhou),NSFC grants 81470711 and 81200760 (Li-Wei Zheng) Ling Ye (Professor, Sate Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University) for financial aid 

主　　题：ageing osteoclastogenesis osteogenesis osteoporosis 

摘      要：Osteoporosis is a serious public bone metabolic disease. However, the mechanisms underlying bone loss combined with ageing, which is known as senile osteoporosis, remains unknown. Here we show the detailed phenotype of this disease caused by SIRT6 knock out （KO） in mice. To the best of our knowledge, this is the first study to reveal that SIRT6 is expressed in both bone marrow stroma cells and bone-related cells in both mouse and human models, which suggests that SIRT6 is an important regulator in bone metabolism. SIRT6-KO mice exhibit a significant decrease in body weight and remarkable dwarfism. The skeleton of the SIRT6-KO mouse is deficient in cartilage and mineralized bone tissue. Moreover, the osteocalcin concentration in blood is lower, which suggests that bone mass is markedly lost. Besides, the tartrate-resistant acid phosphatase 5b （TRAP5b） concentration is much higher, which suggests that bone resorption is overactive. Both trabecular and cortical bones exhibit severe osteopenia, and the bone mineral density is decreased. Moreover, double-labelling analysis shows that bone formation is much slower. To determine whether SIRT6 directly regulates bone metabolism, we cultured primary bone marrow stromal cells for osteogenesis and osteoclastogenesis separately to avoid indirect interference in vivo responses such as inflammation. Taken together, these results show that SIRT6 can directly regulate osteoblast proliferation and differentiation, resulting in attenuation in mineralization. Furthermore, SIRT6 can directly regulate osteoclast differentiation and results in a higher number of small osteoclasts, which may be related to overactive bone resorption.