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.
Highlights
Age-related tendon disorder is one of the main causes of chronic pain, limited joint mobility, and tendon rapture among elderly patients [1, 2]
We compiled all the predicted genes associated with aging, cell differentiation, migration, extracellular matrix (ECM), and proliferation for Venn analysis (Figure 1(c) and Supplementary Table 2), and we found four genes that were related to these functional activities
The results suggested that connective tissue growth factor (CTGF) might be associated with tendon-derived stem/progenitor cells (TSPCs) aging
Summary
Age-related tendon disorder is one of the main causes of chronic pain, limited joint mobility, and tendon rapture among elderly patients [1, 2]. In tendons, aging reduces the number of tendon cells and decreases their activity [3, 4], thereby depleting the resources required to repair injured tendons. Tenocytes were considered to be the only cell type in tendons, which are resident fibroblast-like cells that maintain tendon integrity, remodeling, and repair [4, 6]. TSPCs could express classical stem cell markers, while maintaining the expression of typical tendon-lineage genes, such as scleraxis (SCX) and tenomodulin (TNMD) [10, 11]. Previous studies suggested that TSPCs could promote tendon repair and regeneration and maintain tendon homeostasis [12, 13]. The underlying molecular and cellular mechanisms of TSPC aging remain unclear
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