The Effect of TGF-β3 and IL-1β on L-Type Voltage-Operated Calcium Channels and Calcium Ion Homeostasis in Osteoarthritic Chondrocytes and Human Bone Marrow-Derived Mesenchymal Stem Cells During Chondrogenesis

Background: Transforming growth factor-beta (TGF-beta) and interleukin 1 beta (IL-1 beta) are key regulators of the chondrogenic differentiation, physiology and pathology of cartilage tissue, with TGF-beta promoting chondrogenesis and matrix formation, while IL-1 beta exerts catabolic effects, inhibiting chondrogenesis and contributing to cartilage degradation. Both cytokines alter the intracellular calcium ion (iCa2+) levels; however, the exact pathways are not known. Objectives: This study aimed to evaluate the impact of TGF-beta 3 and IL-1 beta on calcium homeostasis in human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and chondrocytes during chondrogenesis. Results: TGF-beta 3 increased iCa2+ levels in both hBM-MSCs and chondrocytes. Furthermore, TGF-beta 3 increased the functional activity of L-type voltage-operated calcium channels (L-VOCCs) in hBM-MSCs but not in chondrocytes. TGF-beta 3 and IL-1 beta reduced L-VOCCs subunit CaV1.2 (CACNA1C) gene expression in chondrocytes. In hBM-MSCs, TGF-beta 3 and IL-1 beta increased SERCA pump (ATP2A2) gene expression, while in chondrocytes, this effect was observed only with TGF-beta 3. Conclusions: TGF-beta 3 increases iCa2+ both in osteoarthritic chondrocytes and hBM-MSCs during chondrogenesis. In hBM-MSCs, TGF-beta 3-mediated elevation in iCa2+ is related to the increased functional activity of L-VOCCs. IL-1 beta does not change iCa2+ in osteoarthritic chondrocytes and hBM-MSCs; however, it initiates the mechanisms leading to further downregulation of iCa2+ in both types of cells. The differential and cell-specific roles of TGF-beta 3 and IL-1 beta 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.