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Published on: March 15, 2018
VB5 modulates osteoclast metabolic reprogramming and suppresses differentiation by blocking PKM2 nuclear
Hongming Zhou1,2,3, Hengren Li1, Ming Fu4
1Department of Spine Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.
Vitamin B5 (VB5) supplementation reduced bone loss in osteoporosis models by inhibiting osteoclast differentiation. This occurs via the PANK-CoA-PKM2 pathway, impacting cell metabolism and supporting skeletal health.
Area of Science:
- Biochemistry
- Metabolism
- Bone Biology
Background:
- Osteoporosis involves imbalanced bone remodeling and altered osteoclast metabolism.
- The role of nutritional factors, like Vitamin B5 (VB5), in osteoclast metabolism is not well understood.
- VB5 is a precursor to coenzyme A (CoA), vital for metabolic regulation.
Purpose of the Study:
- To investigate the effect of VB5 on osteoporosis and osteoclast differentiation.
- To elucidate the molecular mechanisms underlying VB5's action in bone metabolism.
Main Methods:
- Ovariectomy (OVX)-induced osteoporosis mouse model with varied VB5 diets.
- Micro-computed tomography and histomorphometry for bone analysis.
- In vitro studies on RAW264.7 cells and BMDMs, metabolic flux analysis, molecular docking, co-immunoprecipitation, and Western blotting.
Main Results:
- VB5 supplementation attenuated OVX-induced bone loss and decreased osteoclast numbers.
- VB5 deficiency worsened bone deterioration.
- VB5 increased intracellular CoA, suppressed osteoclast differentiation via the PANK-CoA-PKM2 axis by reducing PKM2 Y105 phosphorylation and nuclear translocation, and decreased cellular respiration.
Conclusions:
- VB5 inhibits osteoclast differentiation and mitigates estrogen deficiency-induced bone loss.
- The PANK-CoA-PKM2 axis is a potential mechanism linking VB5 to metabolic reprogramming in osteoclasts.
- Findings suggest a connection between vitamin-dependent metabolic pathways and skeletal remodeling.
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