Aging is marked by a gradual deterioration in the structural and functional integrity of organs and tissues, leading to an increased susceptibility to joint diseases. Cartilage degeneration caused by aging is a prevalent factor contributing to osteoarthritis (OA) development, a condition that impacts millions worldwide. The initiation of OA pathology is related to cellular senescence, which contributes to DNA damage, cell cycle repression, and the chronic level of inflammation. These senescent stem cells within knee joints are resistant to apoptosis, which display an altered secretion profile and diminished regenerative capacities. The development of interventions aimed at delaying the aging process offers promising avenues for alleviating the burden of age-related pathologies and enhancing health span. Among emerging strategies, gene therapy by engineering cells has gained considerable attention as a transformative modality, utilizing advanced gene editing and delivery technologies to modulate the molecular mechanisms underlying aging. However, specific deletion of p16 (a senescent marker) in chondrocytes did not inhibit the increased production of senescence-associated secretory phenotype factors during cartilage aging. Thus, identification of specific senescent subpopulations in cartilage aging and the development of new strategies focusing on rejuvenating or regenerating senescent chondrocytes are important for the OA management.

This Research Topic aims to identify and characterize the molecular pathways involved in senescence and using engineering methods to edit senescent stem cells to drive endogenous cartilage regeneration. Specifically, we further seek to develop methods that reverse senescence or rejuvenate it to enhance the regenerative potential of cartilage-resident cells. Additionally, the effectiveness of gene engineering of chondrocytes in promoting cartilage repair will be evaluated through both in vitro and in vivo studies. By advancing our knowledge in these areas, we aim to discover transformative therapies for OA.

The scope of this Research Topic encompasses the study of senescent stem cells and the cell engineering approaches that could drive endogenous cartilage regeneration. To gather further insights into engineering senescent chondrocytes, we welcome articles addressing, but not limited to, the following themes:

o Characterization and mechanistic studies of cartilage, infrapatellar fat pad, and synovial membrane-derived stem cells senescence.
o Exploration of sex-related dimorphism in cartilage aging and implications for disease mechanisms and therapeutic responses.
o Development of mechanical modulation approaches for studying mechanisms of senescent chondrocytes in OA.
o Influence of the pericellular and extracellular matrix on cell senescence during OA progression.
o Regenerative strategies utilizing juvenile cartilage-resident stem cells to support joint repair and regeneration.
o Integration of organ-on-chip models to study senescent cellular interactions between different tissue types and the effects of cellular aging in pathological OA contexts.

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Engineering Senescent Chondrocytes for Enhanced Cartilage Regeneration