Regulation of differentiation and generation of osteoclasts in rheumatoid arthritis

Abstract

IntroductionRheumatoid arthritis (RA), which affects nearly 1% of the world’s population, is a debilitating autoimmune disease. Bone erosion caused by periarticular osteopenia and synovial pannus formation is the most destructive pathological changes of RA, also leads to joint deformity and loss of function,and ultimately affects the quality of life of patients. Osteoclasts (OCs) are the only known bone resorption cells and their abnormal differentiation and production play an important role in the occurrence and development of RA bone destruction; this remains the main culprit behind RA.MethodBased on the latest published literature and research progress at home and abroad, this paper reviews the abnormal regulation mechanism of OC generation and differentiation in RA and the possible targeted therapy.ResultOC-mediated bone destruction is achieved through the regulation of a variety of cytokines and cell-to-cell interactions, including gene transcription, epigenetics and environmental factors. At present, most methods for the treatment of RA are based on the regulation of inflammation, the inhibition of bone injury and joint deformities remains unexplored.DiscussionThis article will review the mechanism of abnormal differentiation of OC in RA, and summarise the current treatment oftargeting cytokines in the process of OC generation and differentiation to reduce bone destruction in patients with RA, which isexpected to become a valuable treatment choice to inhibit bone destruction in RA.

Botryococcus terribilis Ethanol Extract Exerts Anti-inflammatory Effects on Murine RAW264 Cells

“…Additionally, chemical/drug perturbation analysis of the downregulated DEGs showed several known Axl inhibitors, such as cabozantinib [ 35 ], iguratimod [ 36 ], fostamatinib [ 37 ], and lapatinib [ 38 ] ( Figure 10 A–D). Finally, gene–disease association enrichment analysis predicts the potential of BTEE in several inflammatory and skin diseases ( Figure 10 E).…”

Exercise and osteoimmunology in bone remodeling

“…15 Stimulating TLR2/4 can directly improve the survival rate of mature osteoclasts. 16 In addition, TLR4 can inhibit osteoblast differentiation by inhibiting the expression of alkaline phosphatase (ALP), osteocalcin (OCN), and Runx2. 17,18 TLR4 inhibits the expression of genes related to osteogenic differentiation, such as Runx2, Sp7, and ATF4, which may also be related to the activation of the ERK MAPK pathway.…”

“…In addition, the TLR2/4 ligand activates the MEK/JNK MAPK signaling pathway through the myeloid differentiation protein 88‐dependent pathway, and increases the expression of RANK in bone marrow stem cells, thus promoting the transformation of bone marrow stem cells into osteoclasts 15 . Stimulating TLR2/4 can directly improve the survival rate of mature osteoclasts 16 . In addition, TLR4 can inhibit osteoblast differentiation by inhibiting the expression of alkaline phosphatase (ALP), osteocalcin (OCN), and Runx2 17,18 .…”

Epigenetic Regulation of Autophagy in Bone Metabolism

“…Elevated levels of SAM can enhance this methylation, ultimately promoting osteoclast differentiation and bone resorption. 30 Deleting DNMT3a in osteoclasts (OC) or using the inhibitor TF-3 in mice protects against bone loss after ovarian removal. 31 Moreover, in multiple myeloma patients, alterations in bone resorption have been associated with elevated IRF8 methylation, induced by myeloma cells’ release of thymidine phosphorylase (TP), leading to decreased IRF8 expression and enhanced bone resorption.…”