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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Bone Marrow Cells, Cartilage, Cell Differentiation, Estradiol, Estrogen Antagonists, Estrogen Receptor alpha, Estrogen Receptor beta, Fulvestrant, Humans, Male, Mesenchymal Stem Cells, Signal Transduction, Young Adult.
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Does estradiol inhibit chondrogenic differentiation of mesenchymal stem cells via nonclassic signaling? Context: We undertook this study to examine the effects of estradiol on chondrogenesis of human bone marrow-derived mesenchymal stem cells (MSCs), with consideration of sex-dependent differences in cartilage repair. Bone marrow was obtained from the iliac crest of young men. Density-gradient centrifugation-separated human MSCs proliferated as a monolayer in serum-containing medium. After confluence was achieved, aggregates were created and cultured in a serum-free differentiation medium. We added different concentrations of 17beta-estradiol (E2) with or without the specific estrogen receptor inhibitor ICI 182.780, membrane-impermeable E2-bovine serum albumin (E2-BSA), ICI 182.780 alone, G-1 (an agonist of G protein-coupled receptor 30 [GPR-30]), and G15 (a GPR-30 antagonist). After 21 days, the aggregates were analyzed histologically and immunohistochemically; we quantified synthesized type II collagen, DNA content, sulfated glycosaminoglycan (sGAG) concentrations, and type X collagen and matrix metalloproteinase 13 (MMP-13) expression. The existence of intracellular and membrane-associated E2 receptors was shown at various stages of chondrogenesis. Smaller aggregates and significantly lower type II collagen and sGAG content were detected after treatment with E2 and E2-BSA in a dose-dependent manner. Furthermore, E2 enhanced type X collagen and MMP-13 expression. Compared with estradiol alone, the coincubation of ICI 182.780 with estradiol enhanced suppression of chondrogenesis. Treatment with specific GPR-30 agonists alone (G-1 and ICI 182.780) resulted in a considerable inhibition of chondrogenesis. In addition, we found an enhancement of hypertrophy by G-1. Furthermore, the specific GPR-30 antagonist G15 reversed the GPR-30-mediated inhibition of chondrogenesis and up-regulation of hypertrophic gene expression.
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The experiments revealed a suppression of chondrogenesis by estradiol via membrane receptors (GPR-30). The study opens new perspectives for influencing chondrogenesis on the basis of classic and nonclassic estradiol signaling. Final Decision: yes