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

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number115497
JournalBone
Volume138
DOIs
Publication statusPublished - 2020 Sep

Bibliographical note

Funding Information:
This work was supported by National Research Foundation of Korea (NRF) Grants funded by the Korean Government ( NRF-2017R1D1A1B03035930 to C.H., NRF-2016R1A5A2008630 to S.J.M.).

Publisher Copyright:
© 2020

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Physiology

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