Palmitoleic acid inhibits RANKL-induced osteoclastogenesis and bone resorption by suppressing NF- B and MAPK signalling pathways

摘要

Osteoclasts are large,multinucleated cells that are responsible for the breakdown or resorptionof bone during bone remodelling. Studies have shown that certain fatty acids (FAs) can increase boneformation, reduce bone loss, and influence total bone mass. Palmitoleic acid (PLA) is a 16-carbon,monounsaturated FA that has shown anti-inflammatory properties similar to other FAs. The effectsof PLA in bone remain unexplored. Here we investigated the effects of PLA on receptor activator ofnuclear factor kappa B (NF- B) ligand (RANKL)-induced osteoclast formation and bone resorption inRAW264.7 murine macrophages. PLA decreased the number of large, multinucleated tartrate resistantacid phosphatase (TRAP) positive osteoclasts and furthermore, suppressed the osteolytic capabilityof these osteoclasts. This was accompanied by a decrease in expression of resorption markers (Trap,matrix metalloproteinase 9 (Mmp9), cathepsin K (Ctsk)). PLA further decreased the expression of genesinvolved in the formation and function of osteoclasts. Additionally, PLA inhibited NF- B activityand the activation of mitogen activated protein kinases (MAPK), c-Jun N-terminal kinase (JNK) andextracellular signal–regulated kinase (ERK). Moreover, PLA induced apoptosis in mature osteoclasts.This study reveals that PLA inhibits RANKL-induced osteoclast formation in RAW264.7 murinemacrophages through suppression of NF- B and MAPK signalling pathways. This may indicate thatPLA has potential as a therapeutic for bone diseases characterized by excessive osteoclast formation.