| Category |
Orthopedics |
| Manuscript Type |
Basic Study |
| Article Title |
Ganagliflozin proline attenuates osteogenic dysfunction and inflammatory signaling during exposure to advanced glycation end products in murine osteoblasts
|
| Manuscript Source |
Unsolicited Manuscript |
| All Author List |
Zhi-Peng Li, Han Li, Jia-Li Xu, Ya-Jing Liu, Dong Li, Peng Wang, Lei Xiang, Shi-Yu Xu, Cheng-Zheng Duan, Sheng-Xin Wang, Jin-Ke Sun, Chang-Jiang Zhang, Dong-Juan He and Cheng Luo |
| Funding Agency and Grant Number |
| Funding Agency |
Grant Number |
| Zhejiang Medical Association Clinical Medical Research Special Fund Project, “Mechanistic study and clinical efficacy observation of SGLT-2 inhibitors in improving type 2 diabetic bone fragility by regulating the AGEs-COL1 axis” |
No. 2025ZYC-Z32 |
| Henan Provincial Key Research and Development Program |
No. 231111311000 |
| Henan Provincial Higher Education Institutions Key Research Project |
No. 26A320038 |
| Henan Provincial Science and Technology Project |
No. 262102310123 |
| Henan Provincial Medical Science and Technology Key Project |
No. LHGJ20250403 |
| Henan Provincial Medical Science and Technology Key Project |
No. LHGJ20220566 |
| Henan Provincial Medical Science and Technology Key Project |
No. LHGJ20240365 |
|
| Corresponding Author |
Cheng Luo, Chief Physician, MD, Professor, Department of Endocrinology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, No. 100 Minjiang Avenue, Kecheng District, Quzhou 324000, Zhejiang Province, China. luochengmi805@wmu.edu.cn |
| Key Words |
Advanced glycation end products; Collagen I; Diabetic bone fragility; Ganagliflozin proline; Nuclear factor kappa B; Osteogenic differentiation; Receptor for advanced glycation end products; Sodium-glucose cotransporter 2 inhibitor |
| Core Tip |
This study demonstrates that ganagliflozin proline (Gana Pro) protects MC3T3-E1 osteoblasts against advanced glycation end product-induced dysfunction. Gana Pro improved proliferation, collagen I expression, osteogenic-marker expression, alkaline phosphatase activity, calcium deposition, and matrix mineralization. These benefits were accompanied by lower receptor for advanced glycation end products (RAGE) expression, p65 phosphorylation, and tumor necrosis factor alpha expression. A separate RAGE-knockdown/phorbol 12-myristate 13-acetate experiment supported the functional involvement of this signaling axis in advanced glycation end products-induced osteogenic suppression. The combined evidence identifies RAGE/nuclear factor kappa B signaling as a plausible mechanistic contributor, although drug-specific pathway mediation requires direct rescue validation. |
| Citation |
Li ZP, Li H, Xu JL, Liu YJ, Li D, Wang P, Xiang L, Xu SY, Duan CZ, Wang SX, Sun JK, Zhang CJ, He DJ, Luo C. Ganagliflozin proline attenuates osteogenic dysfunction and inflammatory signaling during exposure to advanced glycation end products in murine osteoblasts. World J Diabetes 2026; In press
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