Excessive bone marrow adipose tissue (BMAT) is a key contributor to postmenopausal osteoporosis. It is associated with bone marrow-derived mesenchymal stem cells (BM-MSCs), which favor differentiation Show more
Excessive bone marrow adipose tissue (BMAT) is a key contributor to postmenopausal osteoporosis. It is associated with bone marrow-derived mesenchymal stem cells (BM-MSCs), which favor differentiation into adipocytes, thereby compromising osteoblast and bone formation. In addition, BMAT secretes anti-osteogenic factors that exacerbate bone loss. In this study, we investigated the effects of ASPP-092, a diarylheptanoid compound isolated from Curcuma comosa, on BM-MSC differentiation. ASPP-092 inhibited adipogenic differentiation and lipid accumulation by downregulating key adipogenic transcription factors and enzymes, including peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), sterol regulatory element-binding protein 1 (SREBP1), lipoprotein lipase (LPL), and fatty acid-binding protein 4 (FABP4). ASPP-092 also reduced the secretion of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) while increasing anti-inflammatory interleukin-10 (IL-10) and adipokines such as leptin, adiponectin, and resistin. Transcriptomic analysis revealed upregulation of genes involved in the transforming growth factor-beta (TGF-β), Hippo, and Wnt/beta-catenin signaling pathways. Pharmacological inhibition of TGF-β/SMAD2/3 signaling abolished the anti-adipogenic effects of ASPP-092. These findings identify a novel mechanism by which ASPP-092 suppresses BMAT formation and supports its potential as an anti-osteoporotic agent. Show less
Breast cancer is the most frequently diagnosed malignancy among women, resulting from abnormal proliferation of mammary epithelial cells. The highly vascularized nature of breast tissue leads to a hig Show more
Breast cancer is the most frequently diagnosed malignancy among women, resulting from abnormal proliferation of mammary epithelial cells. The highly vascularized nature of breast tissue leads to a high incidence of breast cancer metastases, resulting in a poor survival rate. Previous studies suggest that human mesenchymal stem cells (hMSCs) play essential roles in the growth, metastasis, and drug responses of many cancers, including breast cancer. However, hMSCs from different sources may release different combinations of cytokines that affect breast cancer differently. In this study, we have isolated hMSCs from the placenta (PL-hMSCs) and the chorion (CH-hMSCs) and determined how these hMSCs affect the proliferation, migration, invasion, and gene expression of two human breast cancer cells, MCF-7 and MDA-MB-231, as well as the possible mechanisms underlying those effects. The results showed that the soluble factors derived from PL-hMSCs and CH-hMSCs inhibited the proliferation of MCF-7 and MDA-MB-231 cells but increased the migration of MDA-MB-231 cells. The study of gene expression showed that PL-hMSCs and CH-hMSCs downregulated the expression levels of the protooncogene Our study suggests that CH-hMSCs and PL-hMSCs inhibited breast cancer cell proliferation by negatively regulating Show less