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bioRxiv · 10.64898/2026.11.03.764030

Compartment-Resolved Matrisome Shifts During Postnatal Tendon Maturation in Mice

Peterson, B. E.·Ceja Galindo, D.·McCabe, M. C.·Galloway, J. L.
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Abstract

Tendons acquire their load-bearing capacity during the first month of postnatal growth, driven by the extensive remodeling of the extracellular matrix (ECM). While the role of specific individual components to this process have been well characterized, a comprehensive assessment of how the tendon matrisome changes during this critical window is lacking. This, in part, is due to the challenges associated with solubilization of mature ECM, which is underrepresented by conventical proteomic approaches. To address this, we performed compartment-resolved proteomics on murine Achilles and plantaris tendons at postnatal days 0 (P0), P14, and P28. Sequential extraction methods leveraged a CHAPS-soluble fraction, capturing cellular and soluble matrisome proteins, from the insoluble mature ECM fraction, solubilized by guanidine hydrochloride and hydroxylamine hydrochloride and separately analyzed by label-free quantitative LC-MS/MS. Analysis shows that the two compartments followed distinct trajectories during maturation. The insoluble matrix was dominated by collagenous proteins, which increased from 95% to over 99% of the identified signal intensity, and its composition was largely established by P14. Within the soluble matrisome compartment, collagens increased from 50% to over 60% by P14, accompanied by dynamic regulation of proteins implicated in collagen processing (P4HA1, PCOLCE), crosslinking (LOX, LOXL2), and regulators of collagen fibril assembly and growth (DCN, BGN, FMOD, THBS3, THBS4). Beyond these established regulators, we observed dynamic regulation of less-characterized fibril-associated proteoglycans (KERA, OGN, CHAD), matricellular (COMP, POSTN, MATN2), and angiogenic regulatorily proteins (SERPINF1, ECM1). Together, this work establishes a comprehensive protein-level reference for postnatal tendon maturating, provides new insights into the molecular regulation of functional tendon development.

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Peterson, B. E., Ceja Galindo, D., McCabe, M. C., Galloway, J. L.. 2026-11-05. Compartment-Resolved Matrisome Shifts During Postnatal Tendon Maturation in Mice. https://doi.org/10.64898/2026.11.03.764030

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