Academic Journal
SIRT6-PAI-1 axis is a promising therapeutic target in aging-related bone metabolic disruption
| Title: | SIRT6-PAI-1 axis is a promising therapeutic target in aging-related bone metabolic disruption |
|---|---|
| Authors: | Alkebaier Aobulikasimu, Tao Liu, Jinying Piao, Shingo Sato, Hiroki Ochi, Atsushi Okawa, Kunikazu Tsuji, Yoshinori Asou |
| Source: | Scientific Reports, Vol 13, Iss 1, Pp 1-16 (2023) |
| Publisher Information: | Nature Portfolio, 2023. |
| Publication Year: | 2023 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | Medicine, Science |
| More Details: | Abstract The mechanistic regulation of bone mass in aged animals is poorly understood. In this study, we examined the role of SIRT6, a longevity-associated factor, in osteocytes, using mice lacking Sirt6 in Dmp-1-expressing cells (cKO mice) and the MLO-Y4 osteocyte-like cell line. cKO mice exhibited increased osteocytic expression of Sost, Fgf23 and senescence inducing gene Pai-1 and the senescence markers p16 and Il-6, decreased serum phosphate levels, and low-turnover osteopenia. The cKO phenotype was reversed in mice that were a cross of PAI-1-null mice with cKO mice. Furthermore, senescence induction in MLO-Y4 cells increased the Fgf23 and Sost mRNA expression. Sirt6 knockout and senescence induction increased HIF-1α binding to the Fgf23 enhancer sequence. Bone mass and serum phosphate levels were higher in PAI-1-null aged mice than in wild-type mice. Therefore, SIRT6 agonists or PAI-1 inhibitors may be promising therapeutic options for aging-related bone metabolism disruptions. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-023-33297-7 |
| Access URL: | https://doaj.org/article/d194b5107db345eb9a57e9816ffdca71 |
| Accession Number: | edsdoj.194b5107db345eb9a57e9816ffdca71 |
| Database: | Directory of Open Access Journals |
| Full text is not displayed to guests. | Login for full access. |
| ISSN: | 20452322 |
|---|---|
| DOI: | 10.1038/s41598-023-33297-7 |
| Published in: | Scientific Reports |
| Language: | English |