Empagliflozin ameliorates the impaired osteogenic differentiation ability of adipose-derived stem cells in diabetic osteoporosis by activating autophagy

Shuanglin Yang; Ya Lin; Yuping Xie; Ting Fu; Tianli Wu; Xiaorong Lan; Fangzhi Lou; Jingang Xiao

doi:10.1093/stmcls/sxae019

Empagliflozin ameliorates the impaired osteogenic differentiation ability of adipose-derived stem cells in diabetic osteoporosis by activating autophagy

Stem Cells. 2024 Feb 23:sxae019. doi: 10.1093/stmcls/sxae019. Online ahead of print.

Authors

Shuanglin Yang^{1

2

3}, Ya Lin³, Yuping Xie¹, Ting Fu^{1

3}, Tianli Wu^{1

3}, Xiaorong Lan³, Fangzhi Lou^{1

3}, Jingang Xiao^{1

3

4}

Affiliations

¹ Department of Oral Implantology, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou 646000, China.
² Department of Oral Implantology, Chongqing University Three Gorges Hospital, Chongqing 404100, China.
³ Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Luzhou 646000, China.
⁴ Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou 646000, China.

PMID: 38393380
DOI: 10.1093/stmcls/sxae019

Abstract

Adipose-derived stem cells (ASCs) from diabetic osteoporosis (DOP) mice showed impaired osteogenic differentiation capacity. Recent studies have shown that in addition to antidiabetic drugs, sodium-glucose co-transporter inhibitor-2 (SGLT-2), empagliflozin, can play multipotent roles through various mechanisms of action. In this study, we aimed to investigate the effects and underlying mechanisms of empagliflozin on osteogenic differentiation of ASCs in DOP mice. Our results showed that osteogenic differentiation potential and autophagy activity weakened in DOP-ASCs when compared to controls. However, empagliflozin enhanced autophagy flux by promoting the formation of autophagosomes and acidification of autophagic lysosomes, resulting in an increase in LC3-II expression and a decrease in SQSTM1 expression. Furthermore, empagliflozin contributed to the reversal of osteogenesis inhibition in DOP-ASCs induced by a diabetic microenvironment. When 3-methyladenine was used to block autophagy activity, empagliflozin could not exert its protective effect on DOP-ASCs. Nonetheless, this study demonstrated that the advent of cellular autophagy attributed to the administration of empagliflozin could ameliorate the impaired osteogenic differentiation potential of ASCs in DOP mice. This finding might be conducive to the application of ASCs transplantation for promoting bone fracture healing and bone regeneration in DOP patients.

Keywords: Adipose-derived stem cells; Autophagy; Diabetic osteoporosis; Empagliflozin; Osteogenic differentiation.