PCAT‐1′ s role in wound healing impairment: Mitochondrial dysfunction and bone marrow stem cell differentiation inhibition via PKM2/β‐catenin pathway and its impact on implant osseo‐integration
This study focused on unravelling the role of PCAT‐1 in wound‐healing process, particularly its impact on regenerative and osteogenic abilities of mesenchymal stem cells (MSCs). We delved into how PCAT‐1 regulates mitochondrial oxidative phosphorylation (OXPHOS) and interacts with pivotal molecular...
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Published in | International wound journal Vol. 21; no. 4; pp. e14589 - n/a |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.04.2024
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Subjects | |
Online Access | Get full text |
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Summary: | This study focused on unravelling the role of PCAT‐1 in wound‐healing process, particularly its impact on regenerative and osteogenic abilities of mesenchymal stem cells (MSCs). We delved into how PCAT‐1 regulates mitochondrial oxidative phosphorylation (OXPHOS) and interacts with pivotal molecular pathways, especially β‐catenin and PKM2, using human bone marrow‐derived MSCs. MSCs were cultured under specific conditions and PCAT‐1 expression was modified through transfection. We thoroughly assessed several critical parameters: MSC proliferation, mitochondrial functionality, ATP production and expression of wound healing and osteogenic differentiation markers. Further, we evaluated alkaline phosphatase (ALP) activity and mineral deposition, essential for bone healing. Our findings revealed that overexpressing PCAT‐1 significantly reduced MSC proliferation, hampered mitochondrial performance and lowered ATP levels, suggesting the clear inhibitory effect of PCAT‐1 on these vital wound‐healing processes. Additionally, PCAT‐1 overexpression notably decreased ALP activity and calcium accumulation in MSCs, crucial for effective bone regeneration. This overexpression also led to the reduction in osteogenic marker expression, indicating suppression of osteogenic differentiation, essential in wound‐healing scenarios. Moreover, our study uncovered a direct interaction between PCAT‐1 and the PKM2/β‐catenin pathway, where PCAT‐1 overexpression intensified PKM2 activity while inhibiting β‐catenin, thereby adversely affecting osteogenesis. This research thus highlights PCAT‐1's significant role in impairing wound healing, offering insights into the molecular mechanisms that may guide future therapeutic strategies for enhancing wound repair and bone regeneration. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1742-4801 1742-481X |
DOI: | 10.1111/iwj.14589 |