Shelest Anastasiia, Alaburda Aidas, Vaiciuleviciute Raminta, Uzieliene Ilona, Bialaglovyte Paulina, Bernotiene Eiva
Institute of Biosciences, Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania.
Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania.
Pharmaceutics. 2025 Mar 7;17(3):343. doi: 10.3390/pharmaceutics17030343.
Transforming growth factor-β (TGF-β) and interleukin 1β (IL-1β) are key regulators of the chondrogenic differentiation, physiology and pathology of cartilage tissue, with TGF-β promoting chondrogenesis and matrix formation, while IL-1β exerts catabolic effects, inhibiting chondrogenesis and contributing to cartilage degradation. Both cytokines alter the intracellular calcium ion (iCa) levels; however, the exact pathways are not known. This study aimed to evaluate the impact of TGF-β3 and IL-1β on calcium homeostasis in human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and chondrocytes during chondrogenesis. TGF-β3 increased iCa levels in both hBM-MSCs and chondrocytes. Furthermore, TGF-β3 increased the functional activity of L-type voltage-operated calcium channels (L-VOCCs) in hBM-MSCs but not in chondrocytes. TGF-β3 and IL-1β reduced L-VOCCs subunit CaV1.2 () gene expression in chondrocytes. In hBM-MSCs, TGF-β3 and IL-1β increased SERCA pump () gene expression, while in chondrocytes, this effect was observed only with TGF-β3. TGF-β3 increases iCa both in osteoarthritic chondrocytes and hBM-MSCs during chondrogenesis. In hBM-MSCs, TGF-β3-mediated elevation in iCa is related to the increased functional activity of L-VOCCs. IL-1β does not change iCa in osteoarthritic chondrocytes and hBM-MSCs; however, it initiates the mechanisms leading to further downregulation of iCa in both types of cells. The differential and cell-specific roles of TGF-β3 and IL-1β in the calcium homeostasis of osteoarthritic chondrocytes and hBM-MSCs during chondrogenesis may provide a new insight into future strategies for cartilage repair and osteoarthritis treatment.
转化生长因子-β（TGF-β）和白细胞介素1β（IL-1β）是软骨组织软骨形成分化、生理和病理过程的关键调节因子，TGF-β促进软骨形成和基质形成，而IL-1β发挥分解代谢作用，抑制软骨形成并导致软骨降解。两种细胞因子都会改变细胞内钙离子（iCa）水平；然而，确切途径尚不清楚。本研究旨在评估TGF-β3和IL-1β在软骨形成过程中对人骨髓间充质干细胞（hBM-MSCs）和软骨细胞钙稳态的影响。TGF-β3增加了hBM-MSCs和软骨细胞中的iCa水平。此外，TGF-β3增加了hBM-MSCs中L型电压门控钙通道（L-VOCCs）的功能活性，但在软骨细胞中未增加。TGF-β3和IL-1β降低了软骨细胞中L-VOCCs亚基CaV1.2（）基因的表达。在hBM-MSCs中，TGF-β3和IL-1β增加了SERCA泵（）基因的表达，而在软骨细胞中，仅TGF-β3观察到这种作用。在软骨形成过程中，TGF-β3在骨关节炎软骨细胞和hBM-MSCs中均增加iCa。在hBM-MSCs中，TGF-β3介导的iCa升高与L-VOCCs功能活性增加有关。IL-1β在骨关节炎软骨细胞和hBM-MSCs中不改变iCa；然而，它启动了导致两种类型细胞中iCa进一步下调的机制。TGF-β3和IL-1β在软骨形成过程中对骨关节炎软骨细胞和hBM-MSCs钙稳态的差异和细胞特异性作用可能为未来软骨修复和骨关节炎治疗策略提供新的见解。
