Abstract
Capric acid is a second medium-chain fatty acid, and recent studies have shown that fatty acids are associated with bone density and reduce bone turnover. In this study, we investigated the effects of capric acid on lipopolysaccharide (LPS)-induced osteoclastogenesis in RAW264.7 cells. After treatment with capric acid (1 mM), the number of tartrate resistant acid phosphatase (TRAP)-positive cells decreased significantly. Capric acid reduced LPS-induced TRAP expression, an osteoclast differentiation marker, without inhibiting cell viability. LPS strongly upregulated inducible nitric oxide synthase (iNOS) mRNA levels and nitric oxide (NO) production, whereas capric acid inhibited them. Furthermore, capric acid also inhibited monocyte chemoattractant protein-1 (MCP-1) mRNA expression. Subsequently, we investigated various intracellular signaling proteins, including nuclear factor-κB (NF-κB), c-Jun-N-terminal kinase (JNK), extracellular signal regulated kinase 1/2 (ERK1/2), and signal transducer and activator of transcription 1 (STAT1) and STAT3 associated with osteoclastogenesis. Capric acid had no effects on LPS-induced activation of the NF-κB, JNK, ERK1/2, and STAT1 pathways. However, capric acid inhibited LPS-induced phosphorylation of Ser727 in STAT3. Additionally, stattic (a STAT3 inhibitor) inhibited LPS-induced iNOS and MCP-1 gene expression. In conclusion, we demonstrated that capric acid inhibited LPS-induced osteoclastogenesis by suppressing NO production via the STAT3 pathway. These results suggest that capric acid has important therapeutic implications for treating bone diseases associated with excessive osteoclastogenesis.
Highlights
Osteoclasts are mainly derived from bone marrow hematopoietic monocyte/macrophage lineages
Because monocyte chemoattractant protein-1 (MCP-1) is reportedly involved in osteoclast cell-cell fusion and differentiation, we examined the effects of capric acid on LPS-induced expression of inducible nitric oxide synthase (iNOS) and MCP-1 by RT-PCR [30]
The results showed that LPS-induced iNOS and MCP1 gene expression was inhibited by stattic
Summary
Osteoclasts are mainly derived from bone marrow hematopoietic monocyte/macrophage lineages. NO is a short-lived free radical involved in the regulation of many physiological processes such as vascular relaxation, neurotransmission, platelet aggregation, and the immune response [8,9]. It is generated from oxygen and L-arginine by nitric oxide synthase (NOS). Three isoforms of NOS have been identified: a neuronal form (nNOS or NOS1), an endothelial form (eNOS or NOS3), and an inducible form (iNOS or NOS2) Among these three NOS, iNOS is expressed in response to various inflammatory stimuli and results in the production of a large amount of NO by macrophages during inflammation [10,11]. Recent studies have reported that lipopolysaccharide (LPS) induces osteoclast differentiation and increases bone loss [12]
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