Abstract
Osteoclasts are large, multinucleated cells that are responsible for the breakdown or resorption of bone during bone remodelling. Studies have shown that certain fatty acids (FAs) can increase bone formation, 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 effects of PLA in bone remain unexplored. Here we investigated the effects of PLA on receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast formation and bone resorption in RAW264.7 murine macrophages. PLA decreased the number of large, multinucleated tartrate resistant acid phosphatase (TRAP) positive osteoclasts and furthermore, suppressed the osteolytic capability of 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 genes involved in the formation and function of osteoclasts. Additionally, PLA inhibited NF-κB activity and the activation of mitogen activated protein kinases (MAPK), c-Jun N-terminal kinase (JNK) and extracellular signal–regulated kinase (ERK). Moreover, PLA induced apoptosis in mature osteoclasts. This study reveals that PLA inhibits RANKL-induced osteoclast formation in RAW264.7 murine macrophages through suppression of NF-κB and MAPK signalling pathways. This may indicate that PLA has potential as a therapeutic for bone diseases characterized by excessive osteoclast formation.
Highlights
Bone resorption and formation are tightly coupled in healthy individuals in a process known as bone remodelling [1]
We investigated the effects of Palmitoleic acid (PLA) on RANKL-induced osteoclast formation in RAW264.7 murine macrophages
RAW264.7 murine macrophages were differentiated with RANKL for 5 days in the presence of varying concentrations of PLA
Summary
Bone resorption and formation are tightly coupled in healthy individuals in a process known as bone remodelling [1]. When there is an imbalance between formation and resorption, many bone pathologies may arise such as osteoporosis, osteopetrosis, and rheumatoid arthritis [2]. There are three main bone cell types involved in bone remodelling namely; osteocytes; osteoblasts, and osteoclasts. Osteocytes remain embedded within the mineralized matrix of bone and are thought to translate mechanical loading into biochemical signals that affect bone remodelling [3]. Osteoblasts are responsible for the synthesis and mineralization of bone as well as modulating the differentiation of osteoclasts [4]. Osteoclasts are large, multinucleated cells that are responsible for the resorption of bone
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