Osteoporosis is a chronic inflammatory condition that is characterized by the loss of bone mineral density (BMD). The current study was undertaken to evaluate the impact of onion juice intake on the bone mineral density (BMD) and bone loss in corroboration with antioxidant effects in human (in vivo) as well as inhibitory effects on the differentiation of osteoclasts in the cell line (in vitro). For in vitro studies, the RAW 264.7 (osteoclast progenitor) cells were used to examine the anti-osteoclastogenic effect of onion. In the case of in vivo studies, twenty-four subjects were divided into two groups and advised to intake 100 mL of onion juice or placebo for 8 weeks. Anthropometric measurements and blood samples were collected at the initial, 2(nd), 6(th), 8(th) and 10(th) week. The result of in vitro studies indicated that onion extract would effectively inhibit the osteoclastogenesis and its differentiation. Significant changes in the levels of alkaline phosphatase (ALP), free radicals, total antioxidant capacity (TEAC) and various antioxidants were observed in onion administered subjects. The BMD of three postmenopausal women was also found to be mildly improved on supplementation with onion juice. Onion juice consumption showed a positive modulatory effect on the bone loss and BMD by improving antioxidant activities and thus can be recommended for treating various bone-related disorders, especially osteoporosis.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common types of arthritis. Both are characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. miRNAs play critical roles in the disease processes of arthritic disorders. However, little is known about the effects of miRNAs on critical inflammatory cytokine production with OA and RA progression. Here, we found higher levels of proinflammatory cytokines including interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in human OA and RA synovial fibroblasts (SFs) compared with normal SFs. Searches of open-source microRNA (miRNA) software determined that miR-let-7c-5p and miR-149-5p interfere with IL-1β, IL-6 and TNF-α transcription; levels of all three proinflammatory cytokines were lower in human OA and RA patients compared with normal controls. Anti-inflammatory agents dexamethasone, celecoxib and indomethacin reduced proinflammatory cytokine production by promoting the expression of miR-let-7c-5p and miR-149-5p. Similarly, ibuprofen and methotrexate also enhanced miR-let-7c-5p and miR-149-5p expression in human SFs. The evidence suggests that increasing miR-let-7c-5p and miR-149-5p expression is a novel strategy for OA and RA.

Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. Vascular endothelial growth factor (VEGF) stimulation of endothelial progenitor cells (EPCs) facilitates angiogenesis and the progression of RA. Phosphorylation of sphingosine kinase 1 (SphK1) produces sphingosine-1-phosphate (S1P), which increases inflammatory cytokine production, although the role of S1P in RA angiogenesis is unclear. In this study, we evaluated the impact of S1P treatment on VEGF-dependent angiogenesis in osteoblast-like cells (MG-63 cells) and the significance of SphK1 short hairpin RNA (shRNA) on S1P production in an in vivo model. We found significantly higher levels of S1P and VEGF expression in synovial fluid from RA patients compared with those with osteoarthritis by ELISA analysis. Treating MG-63 cells with S1P increased VEGF production, while focal adhesion kinase (FAK) and Src siRNAs and inhibitors decreased VEGF production in S1P-treated MG-63 cells. Conditioned medium from S1P-treated osteoblasts significantly increased EPC tube formation and migration by inhibiting miR-16-5p synthesis via proto-oncogene tyrosine-protein kinase src (c-Src) and FAK signaling in chick chorioallantoic membrane (CAM) and Matrigel plug assays. Infection with SphK1 shRNA reduced angiogenesis, articular swelling and cartilage erosion in the ankle joints of mice with collagen-induced arthritis (CIA). S1P appears to have therapeutic potential in RA treatment.