Osteoarthritis (OA) is a major joint disease in which inflammatory cytokine interleukin-1β (IL-1β) and matrix metalloproteinases (MMPs) play a pivotal role. Isoliquiritigenin has been reported to have anti-inflammation activity. In this study, the effect of isoliquiritigenin on IL-1β-induced production of matrix metalloproteinase and nuclear factor κB (NF-κB) activation was analyzed. We treated primary cultured articular chondrocytes with isoliquiritigenin and the expressions of MMPs were analyzed on mRNA and protein level. The phosphorylation of IκBa and p65 was analyzed to detect NF-κB activation. We also used in vivo model by treating mice with isoliquiritigenin and detecting the level of MMPs. IL-1β induced NF-κB activation and MMP-1, MMP-3, MMP-9, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 production on chondrocytes. A 10-μM isoliquiritigenin treatment significantly inhibited IL-1β-induced NF-κB activation and these MMPs production on chondrocytes. Injecting isoliquiritigenin into rat knee joint also inhibited IL-1β-induced NF-κB activation and MMPs production in articular cartilage. Isoliquiritigenin treatment inhibited IL-1β-induced MMPs production and NF-κB activation both in vitro and in vivo, suggesting a potential therapeutic role of isoliquiritigenin to treat osteoarthritis.

Background: Thiazide diuretics may improve bone mineral density. However, results are inconsistent for studies evaluating the association between thiazides and risk of osteoporotic fracture. We performed an updated meta-analysis of cohort studies to determine the association between thiazides use and fracture risk. Methods: Relevant studies were identified via systematic search of PubMed and Embase. A random-effect model was used for meta-analysis. Subgroup analyses were performed to explore the potential influences of study characteristics on the outcome. Results: Seventeen cohort studies with 3,537,504 participants were included. The pooled results showed that use of thiazide diuretics at baseline did not significantly affect the risk of overall osteoporotic fracture incidence as compared with controls (risk ratio [RR]: 0.96, 95% confidence interval [CI]: 0.83 to 1.09, p = 0.51) with significant heterogeneity (p for Cochrane's Q test < 0.001, I2 = 90%). Results of subgroup analyses indicated that general status of the participants may be an important determinant for the association between thiazide diuretics and subsequent risk of osteoporotic fracture. Use of thiazide diuretics was associated with significantly reduced risk of fracture in patients with acute status including new-onset stroke or spinal cord injury (RR: 0.70, 95% CI: 0.57 to 0.86, p < 0.001), but not in those with good conditions such as community-dwelling population or hypertensive patients (p for subgroup difference = 0.02). Conclusions: Use of thiazide diuretics is not associated with significantly affected risk of overall osteoporotic fracture. However, the association may be different according to the general status of the participants.

The present study assessed whether microRNA (miR)‑27a is an influential factor in steroid‑induced osteonecrosis of the femoral head (ONFH) and investigated the underlying mechanism of action. The results indicated that serum miR‑27a was decreased in a rat model of ONFH compared with that in control rats. It was also observed that increased miR‑27a expression promoted osteogenic differentiation and cell proliferation, inhibited caspase‑3/9 and B‑cell lymphoma‑2‑associated X protein expression and induced alkaline phosphatase (ALP) activity and bone morphogenetic protein (BMP)‑2, runt‑related transcription factor (Runx)2 and osteonectin mRNA expression in osteoblastic MC3T3‑E1 cells. miR‑27a mimics also induced transforming growth factor (TGF)‑β and Smad7 protein expression in MC3T3‑E1 cells. Furthermore, transfection with TGF‑β expression plasmid was able to enhance the effects of miR‑27a mimics on osteoblastic differentiation, cell proliferation, ALP activity, BMP‑2, Runx2 and osteonectin mRNA expression, and Smad7 protein expression in the MC3T3‑E1 cells. Transfection with a TGF‑β or Smad7 expression plasmid also enhanced the effects of miR‑27a mimics on osteoblastic differentiation, cell proliferation, ALP activity and osteonectin mRNA expression in the MC3T3‑E1 cells. Taken together, the results of the present study suggested that the induction of TGF‑β/Smad7 signaling in osteoblasts may be a potential mechanism by which miR‑27a regulates steroid‑induced ONFH.