The potential mechanism of hypoxia-induced tenogenic differentiation of mesenchymal stem cell for tendon regeneration

Zulkifli, Amirah and Ahmad, Raja Elina and Krishnan, Shaliny and Kong, Peggy and Nam, Hui Yin and Kamarul, Tunku (2023) The potential mechanism of hypoxia-induced tenogenic differentiation of mesenchymal stem cell for tendon regeneration. Tissue & Cell, 82. ISSN 0040-8166, DOI

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Tendon injuries account up to 50% of all musculoskeletal problems and remains a challenge to treat owing to the poor intrinsic reparative ability of tendon tissues. The natural course of tendon healing is very slow and often leads to fibrosis and disorganized tissues with inferior biomechanical properties. Mesenchymal stem cells (MSC) therapy is a promising alternative strategy to augment tendon repair due to its proliferative and multilineage differentiation potential. Hypoxic conditioning of MSC have been shown to enhance their tenogenic differentiation capacity. However, the mechanistic pathway by which this is achieved is yet to be fully defined. A key factor involved in this pathway is hypoxia-inducible factor-1-alpha (HIF-1 alpha). This review aims to discuss the principal mechanism underlying the enhancement of MSC tenogenic differentiation by hypoxic conditioning, particularly the central role of HIF-1 alpha in mediating activation of tenogenic pathways in the MSC. We focus on the interaction between HIF-1 alpha with fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta 1 (TGF beta 1) in regulating MSC tenogenic differentiation pathways in hypoxic conditions. Strategies to promote stabilization of HIF-1 alpha either through direct manipulation of oxygen tension or the use of hypoxia mimicking agents are therefore beneficial in increasing the efficacy of MSC therapy for tendon repair.

Item Type: Article
Uncontrolled Keywords: Hypoxia; Mesenchymal stem cells (MSC); Tenogenic differentiation; Tendon; Signal transduction
Subjects: R Medicine
R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
Divisions: Faculty of Medicine
Faculty of Medicine > Orthopaedic Surgery Department
Faculty of Medicine > Physiology Department
Depositing User: Ms Zaharah Ramly
Date Deposited: 01 Dec 2023 13:17
Last Modified: 01 Dec 2023 13:17

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