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
<b>Background:</b> 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, inhibit...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/17/3/343 |
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| Summary: | <b>Background:</b> 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<sup>2+</sup>) levels; however, the exact pathways are not known. <b>Objectives:</b> 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. <b>Results:</b> TGF-β3 increased iCa<sup>2+</sup> 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 (<i>CACNA1C</i>) gene expression in chondrocytes. In hBM-MSCs, TGF-β3 and IL-1β increased SERCA pump (<i>ATP2A2</i>) gene expression, while in chondrocytes, this effect was observed only with TGF-β3. <b>Conclusions:</b> TGF-β3 increases iCa<sup>2+</sup> both in osteoarthritic chondrocytes and hBM-MSCs during chondrogenesis. In hBM-MSCs, TGF-β3-mediated elevation in iCa<sup>2+</sup> is related to the increased functional activity of L-VOCCs. IL-1β does not change iCa<sup>2+</sup> in osteoarthritic chondrocytes and hBM-MSCs; however, it initiates the mechanisms leading to further downregulation of iCa<sup>2+</sup> 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. |
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| ISSN: | 1999-4923 |