Abstract
Osteoclast, which mediates overactive bone resorption, is one of the key factors for bone destruction in rheumatoid arthritis (RA). Existing studies have shown that abnormal miR-143-3p expression was observed in both RA patients and arthritis animals, which can participate in osteoclast differentiation, and mitogen-activated protein kinase (MAPK) signaling pathway was closely related to osteoclast differentiation. The primary objective of the current study was to determine the role of miR-143-3p in the progression of osteoclast differentiation and its relationship with MAPK signaling pathways. The results showed that miR-143-3p inhibited osteoclast differentiation and decreased the levels of M-CSF and RANKL during osteoclast differentiation. miR-143-3p inhibited the expression of MAPK signaling proteins, which is ERK1/2 in the early stage and JNK in the later stage of osteoclast differentiation. It was also observed that MAPK inhibitors upregulated miR-143-3p expression in osteoclast differentiation. Taken together, our results suggested that miR-143-3p could inhibit the differentiation of osteoclast, which was related to inhibiting MAPK signaling pathways. This may provide a novel strategy for curing RA.
Highlights
rheumatoid arthritis (RA) is a chronic systemic autoimmune disease
The plasma expression of miR-143-3p in RA patients and healthy controls (HCs) was analyzed by qPCR, and the results showed that the expression of miR-143-3p in peripheral blood of RA patients was significantly lower than that of HCs (Figure 1(a))
A scanning electron microscope showed that osteoclasts attached and grew on the bone slices, protruding flaky, or filamentous pseudopodia, and bone resorption lacunae of different sizes appeared on the bone slices, indicating that osteoclasts cocultured with monocytes and synovial fibroblasts had obvious bone resorption function (Figure 1(h))
Summary
It is well known that bone destruction can occur in the early stages of RA. Osteoclast, which can mediate overactive bone resorption, is considered to be one of the key cells that cause bone destruction in RA [1]. Studies have shown that the bone destruction is closely related to synovitis in RA [2]. Synovial cells can secrete various kinds of cytokines such as macrophage colony-stimulating factor (M-CSF) and express osteoclast differentiation factor (ODF)/receptor activator of NF-kappa B ligand (RANKL) [3, 4], which can initiate a variety of intracellular signaling transduction pathways that regulate osteoclast-specific gene expression and transcription including MAPK, thereafter to induce osteoclast differentiation and lead to bone destruction [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
