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Published on: March 22, 2024
CTGF Attenuates Tendon-Derived Stem/Progenitor Cell Aging
Yun-Feng Rui1,2,3,4,5, Min-Hao Chen1,2,3,4,5, Ying-Juan Li5,6
1Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Abstract:
Aged tendon-derived stem/progenitor cells (TSPCs) lead to age-related tendon disorders and impair tendon healing. However, the underlying molecular mechanisms of TSPC aging remain largely unknown. Here, we investigated the role of connective tissue growth factor (CTGF) in TSPC aging. CTGF protein and mRNA levels were markedly decreased in the aged TSPCs. Moreover, recombinant CTGF attenuates TSPC aging and restores the age-associated reduction of self-renewal and differentiation of TSPCs. In addition, cell cycle distribution of aged TSPCs was arrested in the G1/S phase while recombinant CTGF treatment promoted G1/S transition. Recombinant CTGF also rescued decreased levels of cyclin D1 and CDK4 and reduced p27kip1 expression in aged TSPCs. Our results demonstrated that CTGF plays a vital role in TSPC aging and might be a potential target for molecular therapy of age-related tendon disorders.
Insights
Connective tissue growth factor (CTGF) declines in aged tendon stem cells, impairing healing. Supplementing CTGF rejuvenates these cells, offering a potential therapy for age-related tendon disorders.
Area of Science:
- Biogerontology
- Stem Cell Biology
- Musculoskeletal Research
Background:
- Aged tendon-derived stem/progenitor cells (TSPCs) contribute to age-related tendon disorders and impaired healing.
- The molecular mechanisms driving TSPC aging are not well understood.
Purpose of the Study:
- To investigate the role of connective tissue growth factor (CTGF) in the aging process of TSPCs.
- To explore CTGF as a potential therapeutic target for age-related tendon conditions.
Main Methods:
- Quantification of CTGF protein and mRNA levels in aged TSPCs.
- Treatment of aged TSPCs with recombinant CTGF.
- Analysis of TSPC self-renewal, differentiation, and cell cycle progression.
- Assessment of cell cycle regulatory proteins (cyclin D1, CDK4, p27kip1).
Main Results:
- CTGF levels were significantly decreased in aged TSPCs.
- Recombinant CTGF treatment attenuated TSPC aging, restoring self-renewal and differentiation.
- CTGF promoted G1/S phase transition in aged TSPCs arrested in G1/S.
- CTGF treatment normalized cyclin D1 and CDK4 levels while reducing p27kip1 expression.
Conclusions:
- CTGF plays a critical role in TSPC aging.
- CTGF may serve as a potential molecular therapeutic target for age-related tendon disorders and impaired tendon healing.
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