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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| author | Anastasiia Shelest Aidas Alaburda Raminta Vaiciuleviciute Ilona Uzieliene Paulina Bialaglovyte Eiva Bernotiene |
| author_facet | Anastasiia Shelest Aidas Alaburda Raminta Vaiciuleviciute Ilona Uzieliene Paulina Bialaglovyte Eiva Bernotiene |
| author_sort | Anastasiia Shelest |
| collection | DOAJ |
| description | <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. |
| format | Article |
| id | doaj-art-21435ff86d1947be8f2dded8aee006a2 |
| institution | Kabale University |
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| language | English |
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| spelling | doaj-art-21435ff86d1947be8f2dded8aee006a22025-08-20T03:43:34ZengMDPI AGPharmaceutics1999-49232025-03-0117334310.3390/pharmaceutics17030343The 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 ChondrogenesisAnastasiia Shelest0Aidas Alaburda1Raminta Vaiciuleviciute2Ilona Uzieliene3Paulina Bialaglovyte4Eiva Bernotiene5Institute of Biosciences, Life Sciences Center, Vilnius University, LT-10257 Vilnius, LithuaniaInstitute of Biosciences, Life Sciences Center, Vilnius University, LT-10257 Vilnius, LithuaniaDepartment of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, LithuaniaDepartment of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, LithuaniaDepartment of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, LithuaniaDepartment of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania<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.https://www.mdpi.com/1999-4923/17/3/343TGF-βIL-1βintracellular calcium levelsvoltage-operated calcium channelsL-type calcium channelsbone marrow mesenchymal stem cells |
| spellingShingle | Anastasiia Shelest Aidas Alaburda Raminta Vaiciuleviciute Ilona Uzieliene Paulina Bialaglovyte Eiva Bernotiene 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 Pharmaceutics TGF-β IL-1β intracellular calcium levels voltage-operated calcium channels L-type calcium channels bone marrow mesenchymal stem cells |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | TGF-β IL-1β intracellular calcium levels voltage-operated calcium channels L-type calcium channels bone marrow mesenchymal stem cells |
| url | https://www.mdpi.com/1999-4923/17/3/343 |
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