| Title |
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 / |
| Authors |
Shelest, Anastasiia ; Alaburda, Aidas ; Vaičiulevičiūtė, Raminta ; Uzielienė, Ilona ; Bialaglovytė, Paulina ; Bernotienė, Eiva |
| DOI |
10.3390/pharmaceutics17030343 |
| Full Text |
|
| Is Part of |
Pharmaceutics: Special Issue: Osteoarthritis and Cartilage Biologics.. Basel : MDPI. 2025, vol. 17, iss. 3, art. no. 343, p. 1-15.. eISSN 1999-4923 |
| Keywords [eng] |
TGF-β ; IL-1β ; intracellular calcium levels ; voltage-operated calcium channels ; L-type calcium channels ; bone marrow mesenchymal stem cells ; chondrocytes ; chondrogenesis |
| Abstract [eng] |
Background: 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 (iCa2+) levels; however, the exact pathways are not known. Objectives: 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. Results: TGF-β3 increased iCa2+ 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 (CACNA1C) gene expression in chondrocytes. In hBM-MSCs, TGF-β3 and IL-1β increased SERCA pump (ATP2A2) gene expression, while in chondrocytes, this effect was observed only with TGF-β3. Conclusions: TGF-β3 increases iCa2+ both in osteoarthritic chondrocytes and hBM-MSCs during chondrogenesis. In hBM-MSCs, TGF-β3-mediated elevation in iCa2+ is related to the increased functional activity of L-VOCCs. IL-1β 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-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. |
| Published |
Basel : MDPI |
| Type |
Journal article |
| Language |
English |
| Publication date |
2025 |
| CC license |
|
