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Updated: May 9, 2026
Matrix-assisted Autologous Chondrocyte Transplantation for Remodeling and Repair of Chondral Defects in a Rabbit Model
Published on: May 21, 2013
Fibrocartilage repair involves chronic cellular senescence in a rat model of bone marrow stimulation
Luke Childress1,2, Landon B Gatrell1,2, Hong Wu1,2
1Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.
Objective:
Cellular senescence has been implicated in the progression of post-traumatic osteoarthritis, but any role in pre-osteoarthritic cartilage repair is unknown. Our objective was to determine whether senescent cells contribute to fibrocartilage repair using a rodent model of marrow stimulation.
Design:
A 1 mm osteochondral defect was generated in the trochlear groove of young adult and middle-aged Lewis rats, modeling the age range when humans receive marrow stimulation. Some rats were treated by intra-articular (IA) injection of senolytic drugs navitoclax or dasatinib plus quercetin. Repair tissue was characterized during the first months after marrow stimulation by histology as well as bulk and single cell transcriptomic analysis.
Results:
Multiple senescence markers were measured within repair tissue during the first months of repair, in contrast to adjacent, intact articular cartilage. The IA delivery of senolytic drugs reduced p16Ink4a-immunopositive cell numbers but did not promote chondrogenesis. The numbers of p16-positive cells were similar between young adult and middle-aged rats, despite proteoglycan deposition decreasing markedly with age. Bulk RNA sequencing of repair tissue demonstrated sustained upregulation of factors linked to established forms of the senescence-associated secretory phenotype. Single cell RNA sequencing revealed heterogeneity in mesenchymal cells within the early repair tissue, confirmed differences in senescence marker expression between newly-formed chondrocytes and those within adjacent intact cartilage, and established differences in oxidative stress response between these two populations during the chondrogenic phase of repair.
Conclusions:
Senescent cells, including neochondrocytes, are abundant within inferior repair tissue following marrow stimulation. While their fibrogenic SASP is associated with poor healing, their removal after senescence induction does not improve repair tissue quality, possibly due to the lack of a replacement chondrogenic population.
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