Vitamin B5 inhibit RANKL induced osteoclastogenesis and ovariectomy induced osteoporosis by scavenging ROS generation.

B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism. The participation of B vitamins in bone health has been recognized for decades. Pantothenic acid (vitamin B5) is mainly known for its wide variety of sources. However, the potential role of pantothenic acid in bone health and metabolism is still unclear. In this study, we found pantothenic acid has a dual effect on RANKL-induced osteoclastogenesis. Tartrate-resistant acid phosphatase (TRAP) stain shows that osteoclastogenesis was remarkably induced in a lower dosage of pantothenic acid (< 200 mM) and significantly inhibited while the pantothenic acid concentration increases to a certain extent (> 500 mM). We further confirmed this dual effect of pantothenic acid in osteoclastogenesis by detecting osteoclast formation and bone resorption using focal adhesion stain and pit formation, respectively. Mechanistically, we found phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) pathway was activated in pre-osteoclasts (pOCs) after cultured with lower dosage of pantothenic acid; while the ROS generation was eliminated with upregulation of forkhead box O1 (FoxO1), forkhead box O2 (FoxO2) and NF-E2-related factor 2 (Nrf2) in pOCs after cultured with higher dosage of pantothenic acid. Finally, we used ovariectomized (OVX) mice to explore the potential role of pantothenic acid rich dietary in regulating bone metabolism , the result shows that pantothenic acid rich dietary can protect bone loss from estrogen deficiency. In brief, our study identified a new understanding of pantothenic acid in regulating osteoclastogenesis, revealed a therapeutic potential of pantothenic acid in prevention of bone loss related disorders.