Impaired loading following denervation elicits dynamic, differential growth trajectories of musculoskeletal tissues

Sciatic nerve resection in one-day-old mice impairs cumulative Achilles tendon growth, shifting cell proliferation and matrix-driven growth trajectories and altering mechanotransduction programs with age.

• Why it matters: Mechanical forces are crucial for musculoskeletal maintenance, but how biophysical cues shape early postnatal growth and maturation—especially in dense connective tissues—remains unclear.
• What they did: One-day-old mice underwent sciatic nerve resection to denervate hamstrings and distal hindlimb muscles, followed by assessment of gait, transcriptional changes, and Achilles tendon growth trajectories over early postnatal development.
• The result: Denervation causes severe, sustained gait alterations and reduced bone and tendon growth, with Achilles tendon mechanosignaling shifting toward inflammation and matrix catabolism as mice age, informing mechanobiology of developing limbs.

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