The involvement of Bcl-2 family proteins in AKT-regulated cell survival in cisplatin resistant epithelial ovarian cancer

Low-intensity pulsed ultrasound (LIPUS) is a mechanical stimulus that plays a key role in regulating the differentiation of bone marrow mesenchymal stem cells (BMSCs). However, the way in which it affects the chondrogenic differentiation of BMSCs remains unknown. In this study, we aimed to investigate whether LIPUS is able to influence TGF-β1-induced chondrogenesis of BMSCs through the integrin-mechanistic target of the Rapamycin (mTOR) signaling pathway. BMSCs were isolated from rat bone marrow and cultured in either standard or TGF-β1-treated culture medium. BMSCs were then subjected to LIPUS at a frequency of 3 MHz and a duty cycle of 20%, and integrin and mTOR inhibitors added in order to analyze their influence on cell differentiation. BMSCs were phenotypically analyzed by flow cytometry and the degree of chondrogenesis evaluated through toluidine blue staining, immunofluorescence, and immunocytochemistry. Furthermore, expression of COL2, aggrecan, SOX9, and COL1 was assessed by qRT-PCR and western blot analysis. We found that LIPUS promoted TGF-β1-induced chondrogenesis of BMSCs, represented by increased expression of COL2, aggrecan and SOX9 genes, and decreased expression of COL1. Notably, these effects were prevented following addition of integrin and mTOR inhibitors. Taken together, these results indicate that mechanical stimulation combined with LIPUS promotes TGF-β1-induced chondrogenesis of BMSCs through the integrin-mTOR signaling pathway.

Background: Knee osteoarthritis (KOA) is the leading cause of pain and stiffness, affecting older adults’ physical function and quality of life. As a form of mind-body exercise, Tai Chi has been recommended as an exercise prescription for KOA patients. This study examined the effects and continuation of modified Tai Chi exercises on physical function and quality of life in elderly women with KOA.Methods: We conducted a single-blind, randomized controlled trial (RCT) on 40 older women with KOA. The participants were randomized to a 12 weeks Tai Chi or control group. The Tai Chi group attended a kind of modified Tai Chi training sessions three times per week; the control group attended wellness education sessions once a week. The primary outcome was the Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Secondary outcomes were the Berg Balance Scale (BBS), Timed Up and Go (TUG), Short-Form 36 (SF-36), Pittsburgh Sleep Quality of Index (PSQI), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS).Results: After the 12-weeks the Tai Chi group showed significan improvement in the WOMAC pain (mean difference, −5.09 points, p = 0.001), WOMAC stiffness (mean difference, −3.60 points, p = 0.002), WOMAC physical function (mean difference, −11.21 points, p = 0.001) compared to the control group. In addition, the Tai Chi group had also significant improvement in the BBS (mean difference, 1.70 points, p = 0.008), TUG (mean difference, −0.52s, p = 0.001), SF-36PCS (mean difference, 7.60 points, p = 0.001), MCS (mean difference, 7.30 points, p = 0.001), PSQI (mean difference, −3.71 points, p = 0.001), SDS (mean difference, −5.37 points, p = 0.025) and SAS (mean difference, −5.06 points, p = 0.002).Conclusion: The modified Tai Chi exercises are an effective treatment for improved physical function and quality of life in elderly women with KOA.Clinical Trial Registration: The trial was registered in Chinese Clinical Trial Registry (ChiCTR2000040721), http://www.chictr.org.cn/edit.aspx?pid=65419&htm=4.

Low-intensity pulsed ultrasound (LIPUS) can induce mesenchymal stem cell (MSC) differentiation, although the mechanism of its potential effects on chondrogenic differentiation is unknown. Since autophagy is known to regulate the differentiation of MSCs, the aim of our study was to determine whether LIPUS induced chondrogenesis via autophagy regulation. MSCs were isolated from the rat bone marrow, cultured in either standard or chondrogenic medium, and stimulated with 3 MHz of LIPUS given in 20% on–off cycles, with or without prior addition of an autophagy inhibitor or agonist. Chondrogenesis was evaluated on the basis of aggrecan (AGG) organization and the amount of type II collagen (COL2) and the mRNA expression of AGG, COL2, and SRY-related high mobility group-box gene 9 (SOX9) genes. LIPUS promoted the chondrogenic differentiation of MSCs, as shown by the changes in the extracellular matrix (ECM) proteins and upregulation of chondrogenic genes, and these effects were respectively augmented and inhibited by the autophagy inhibitor and agonist. Taken together, these results indicate that LIPUS promotes MSC chondrogenesis by inhibiting autophagy.