title: Phenotypic research on senile osteoporosis caused by SIRT6 deficiency.
abstract: 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.
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: De-Mao
authors.initials: DM
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Di-Xin
authors.initials: DX
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Ruo-Shi
authors.initials: RS
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Ya-Chuan
authors.initials: YC
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Xue-Dong
authors.initials: XD
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001862:Bone Resorption; D001842:Bone and Bones; D002454:Cell Differentiation; D006801:Humans; D051379:Mice; D010006:Osteoblasts; D010010:Osteoclasts; D010012:Osteogenesis; D010024:Osteoporosis / Q000235:genetics*; D010641:Phenotype; D037761:Sirtuins / Q000235:genetics* / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: C501860:Sirt6 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; C516592:SIRT6 protein, human; D037761:Sirtuins