2. Academic Validation
  3. Hyperglycemia differentially regulates osteoblast and osteoclast autophagy via AMPK/mTOR/p70 S6K signaling in diabetic osteoporosis

Hyperglycemia differentially regulates osteoblast and osteoclast autophagy via AMPK/mTOR/p70 S6K signaling in diabetic osteoporosis

  • Mol Cell Endocrinol. 2026 May:615:112739. doi: 10.1016/j.mce.2026.112739.
Bin Zhou 1,  Fen Feng 2,  Cila Zhou 3,  Kuang Yao 3,  Ping Huang 3
Affiliations

Affiliations

  • 1 Department of Endocrinology, The Central Hospital of Shaoyang, Shaoyang, China. Electronic address: [email protected].
  • 2 School of Pharmacy, Shaoyang University, Shaoyang, China.
  • 3 Department of Endocrinology, The Central Hospital of Shaoyang, Shaoyang, China.
PMID: 41611117 DOI: 10.1016/j.mce.2026.112739
Abstract

Type 2 diabetes mellitus (T2DM) often induces diabetic osteoporosis (DOP) with impaired bone remodeling, yet its underlying mechanism remains elusive. This study identified the differential regulatory role of the AMPK/mTOR/p70 S6K signaling axis in bone cell function. In vivo, diabetes reduced AMPK phosphorylation, enhanced mTOR/p70 S6K activation, and diminished Autophagy in rat femoral tissue. In vitro, HG exerted cell-type-specific effects via the AMPK signaling pathway: in osteoblasts, HG inhibited AMPK phosphorylation, activated mTOR/p70 S6K, suppressed Autophagy, and impaired mineralization as well as Alkaline Phosphatase (ALP) activity; conversely, in osteoclasts, HG enhanced Autophagy through the inverse regulatory pathway and accelerated osteoclast differentiation and bone resorption. Collectively, these findings illustrate that hyperglycemia disrupts bone homeostasis via cell-type-specific regulation of AMPK, suggesting that AMPK-mediated Autophagy serves as a potential critical therapeutic target for diabetes-related bone diseases.

Keywords

AMPK; Diabetic osteoporosis; Osteoblast; Osteoclast; autophagy.

Figures
Products