Morroniside attenuates high glucose-induced BMSC dysfunction by regulating the Glo1/AGE/RAGE axis

Area of Science:

• Stem cell biology
• Diabetology
• Pharmacology

Background:

• Type 1 diabetes mellitus (T1DM) impairs bone formation due to high glucose (HG)-induced bone marrow mesenchymal stem cell (BMSC) dysfunction.
• Morroniside, derived from Cornus officinalis, possesses biological activities relevant to cell metabolism and tissue regeneration.
• The precise mechanisms of morroniside's effects on HG-induced BMSC dysfunction are not well understood.

Purpose of the Study:

• To investigate the effects of morroniside on high glucose-induced bone marrow mesenchymal stem cell dysfunction.
• To elucidate the underlying mechanisms, including the role of glyoxalase-1 (Glo1) and advanced glycation end product (AGE)-receptor for advanced glycation end product (RAGE) signaling.
• To evaluate the therapeutic potential of morroniside in a type 1 diabetes mellitus rat model.

Main Methods:

• In vitro assessment of BMSC osteogenesis using alkaline phosphatase (ALP) and Alizarin Red staining.
• Quantitative real-time PCR and Western blot to analyze osteo-specific markers, RAGE signaling, and Glo1 expression.
• In vivo evaluation in a T1DM rat model to assess bone loss and microarchitecture.

Main Results:

• Morroniside treatment reversed HG-impaired BMSC osteogenic differentiation in vitro.
• Morroniside suppressed AGE formation and RAGE expression by activating Glo1.
• In vivo, morroniside attenuated bone loss and improved bone microarchitecture, correlating with Glo1 upregulation and RAGE downregulation.

Conclusions:

• Morroniside mitigates HG-mediated BMSC dysfunction by inhibiting AGE-RAGE signaling and activating Glo1.
• Morroniside demonstrates potential as a therapeutic agent for diabetic osteoporosis.