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Loss of Sirtuin 6 in osteoblast lineage cells activates osteoclasts, resulting in osteopenia

 Sung-Jin Kim  ;  Yongxu Piao  ;  Moon Geon Lee  ;  A Ruem Han  ;  Kyoungeun Kim  ;  Chung-Ju Hwang  ;  Jeong Taeg Seo  ;  Seok Jun Moon 
 BONE, Vol.138 : 115497, 2020-09 
Journal Title
Issue Date
High turnover osteopenia ; Osteoblast ; Osteoclast ; Sirtuin 6
Adult bone homeostasis requires a fine-tuned balance between the activity of osteoblasts and osteoclasts. This osteoblast-osteoclast coupling is therapeutically important because it limits the efficacy of most anabolic or anti-resorptive treatments for osteoporosis. Sirtuin6 (SIRT6), a histone deacetylase, was implicated recently as an important regulator in bone homeostasis, but its in vivo function in osteoblast lineage cells remains unclear, mainly due to a lack of in vivo experiments with osteoblast lineage-specific Sirt6 knockout mice. Here, we show that Sirt6 in mature osteoblasts and/or osteocytes inhibits osteoclastogenesis via a paracrine mechanism. We found that osteoblast/osteocyte-specific Sirt6 knockout mice show reduced bone mass due to increased osteoclast formation. Mechanistically, we attribute this increased osteoclastogenesis to decreased osteoprotegerin expression in Sirt6-null osteoblasts and osteocytes. This loss of Sirt6 in osteoblasts and osteocytes does not, however, alter bone formation parameters in vivo. It does accelerate osteogenic differentiation in ex vivo culture, indicating that the osteoblast/osteocyte-autonomous functions of SIRT6 have minor effects on the osteopenic phenotype. These results establish a critical role for SIRT6 in mature osteoblasts and osteocytes in adult bone homeostasis as a negative paracrine regulator of osteoclastogenesis.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Orthodontics (교정과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
Kim, Sung Jin(김성진) ORCID logo https://orcid.org/0000-0003-4115-0403
Moon, Seok Jun(문석준) ORCID logo https://orcid.org/0000-0001-7282-2888
Seo, Jeong Taeg(서정택) ORCID logo https://orcid.org/0000-0003-2697-0251
Hwang, Chung Ju(황충주) ORCID logo https://orcid.org/0000-0003-3024-4551
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