TY - JOUR TI - Scleraxis-lineage cells are required for tendon homeostasis and their depletion induces an accelerated extracellular matrix aging phenotype AU - Korcari, Antonion AU - Nichols, Anne EC AU - Buckley, Mark R AU - Loiselle, Alayna E A2 - Wan, Mei A2 - Isales, Carlos A2 - Dyment, Nathanial VL - 12 PY - 2023 DA - 2023/01/19 SP - e84194 C1 - eLife 2023;12:e84194 DO - 10.7554/eLife.84194 UR - https://doi.org/10.7554/eLife.84194 AB - Aged tendons have disrupted homeostasis, increased injury risk, and impaired healing capacity. Understanding mechanisms of homeostatic disruption is crucial for developing therapeutics to retain tendon health through the lifespan. Here, we developed a novel model of accelerated tendon extracellular matrix (ECM) aging via depletion of Scleraxis-lineage cells in young mice (Scx-DTR). Scx-DTR recapitulates many aspects of tendon aging including comparable declines in cellularity, alterations in ECM structure, organization, and composition. Single-cell RNA sequencing demonstrated a conserved decline in tenocytes associated with ECM biosynthesis in aged and Scx-DTR tendons, identifying the requirement for Scleraxis-lineage cells during homeostasis. However, the remaining cells in aged and Scx-DTR tendons demonstrate functional divergence. Aged tenocytes become pro-inflammatory and lose proteostasis. In contrast, tenocytes from Scx-DTR tendons demonstrate enhanced remodeling capacity. Collectively, this study defines Scx-DTR as a novel model of accelerated tendon ECM aging and identifies novel biological intervention points to maintain tendon function through the lifespan. KW - aging KW - extracellular matrix KW - Scleraxis KW - tendon JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -