Products Cited in Publications Worldwide Metformin combined with alendronate ameliorates osteoarthritis by attenuating RANKL-induced bone resorption and protecting cartilage against degradation

Metformin combined with alendronate ameliorates osteoarthritis by attenuating RANKL-induced bone resorption and protecting cartilage against degradation

Guo, Yanjing; Yang, Ruijia; Zong, Sujing; Wang, Zhenyu; Zhao, Jiyu; Chen, Chongwei; Wang, Chunfang; Wang, Shaowei

DOI:

Abstract

The purpose of the present study was to investigate the effect of metformin combined with alendronate on subchondral bone and cartilage degeneration in a destabilization of the medial meniscus (DMM)-induced osteoarthritis (OA) mouse model. There were lower OARSI scores and fewer TRAP-positive cells in DMM mice after treatment with metformin combined with alendronate. In cartilage, metformin inhibited the expression of MMP3 and MMP13 in IL-1β-stimulated OA chondrocytes and increased the expression of Sox9 and aggrecan. In parallel, metformin also inhibited cartilage matrix degradation, as shown by Alcian blue staining and SO/FG staining in ATDC5 cells and cartilage tissues. Moreover, metformin and alendronate downregulated the levels of specific genes and proteins (NFATc1, c-Fos, DC-STAMP, TNFRSF11, CTSK), thereby inhibiting osteoclast differentiation in vitro. Mechanistically, metformin increased the expression of phospho-AMPK alpha1, attenuated the phosphorylation of NF-κB, and reduced reactive oxygen species (ROS) levels. Metformin combined with alendronate may be a useful candidate for attenuating early-stage OA. This would be an ideal drug/drug combination for treating osteoarthritis in the presence of osteoporosis combined with T2D.

Keywords

osteoarthritis ; subchondral bone ; cartilage ; metformin ; alendronate

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