Nuciferine prevents bone loss by disrupting multinucleated osteoclast formation and promoting type H vessel formation

Abstract

Recently, type H vessels were reported to couple angiogenesis and osteogenesis during osteoclastogenesis, and tartrate‐resistant acid phosphatase (Trap)+ preosteoclasts were found to secrete increased PDGF‐BB to promote type H vessel formation. Therefore, utilization of type H vessels may be a strategy to treat diseases involving bone loss. In the present study, we found that nuciferine, a natural bioactive compound, has various effects, including inhibiting osteoclastogenesis and promoting type H vessel formation. Nuciferine inhibited osteoclastogenesis and bone resorption but increased the relative number of Trap+ preosteoclasts. Nuciferine restrained the expression of osteoclast‐specific genes and proteins, promoted PDGF‐BB production and potentiated related angiogenic activities by inhibiting the MAPK and NF‐κB signaling pathways in vitro. We confirmed the bone‐protective effects of nuciferine in ovariectomized mice and found that nuciferine treatment increased the PDGF‐BB concentration and the number of type H vessels in the femur. In conclusion, our results demonstrated that nuciferine can decrease multinucleated osteoclast formation and promote type H vessel formation through preservation of Trap+ preosteoclasts via inhibition of the MAPK and NF‐κB signaling pathways and may be an excellent agent for the treatment of diseases involving bone loss.

Regulating Type H Vessel Formation and Bone Metabolism via Bone‐Targeting Oral Micro/Nano‐Hydrogel Microspheres to Prevent Bone Loss

“…Huang et al [ 25 ] reported that Harmine inhibited RANKL‐induced multinucleated osteoclast formation and alleviated bone resorption while inducing type H vessel formation. Likewise, Song et al [ 26 ] reported that Nuciferine suppressed the formation of RANKL‐induced multinucleated osteoclasts by inhibiting mitogen‐activated protein kinase (MAPK) and nuclear factor‐𝜅B (NF‐𝜅B) signaling pathways, preventing the production of multinucleated osteoclasts and increasing type H vessel formation. Intriguingly, DFO inhibits osteoclastogenesis by upregulating HO‐1 via the p38 MAPK signaling pathway.…”

Acacetin Prevents Bone Loss by Disrupting Osteoclast Formation and Promoting Type H Vessel Formation in Ovariectomy-Induced Osteoporosis

“…Mononuclear preosteoclasts can promote the growth of type H vessels by releasing platelet-derived growth factor-BB (PDGF-BB) prior to multinucleated osteoclast formation ( Xiaoqun Li et al, 2020 ). Moreover, the number of type H vessels decreases with age to a degree consistent with the severity of bone loss ( Song et al, 2020 ). Therefore, by simultaneously interrupting the maturation and activation of osteoclasts, inhibiting bone resorption and promoting the formation of type H blood vessels, osteoporosis can be effectively prevented.…”

A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis

“…Recent studies revealed that the number of type-H vessels is apparently reduced in osteoporotic and aged bones, accompanied by a decrease in the number of osteoprogenitors [ 7 , 8 ]. Medications stimulating the formation of type-H vessels have been discovered to prevent bone loss to some extent [ 9 , 10 ]. In combination with these breakthroughs, we aim to develop a bone-targeting therapy for osteoporosis, which can inhibit bone resorption while promoting bone formation and vascularization.…”