Impaired loading following denervation elicits dynamic, differential growth trajectories of musculoskeletal tissues
4 affiliations
- 1McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA.
- 2School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA.
- 3Children’s Hospital of Philadelphia, Philadelphia, PA.
- 4Translational Musculoskeletal Research Laboratory, CMC VA Medical Center, Philadelphia, PA.
Abstract
Physical forces dictate the function and maintenance of adult musculoskeletal tissues. Yet, the impact of biophysical cues on the growth and maturation of these tissues, especially dense connective tissues, remains unclear. Here, we investigated the effects of neonatal mechanical loading on early postnatal growth of the musculoskeletal tissues of the lower limb, with particular focus on the Achilles tendon. We performed sciatic nerve resection (SNR) on one-day-old mice to denervate the hamstrings and distal hindlimb muscles. Sciatic Nerve Resection resulted in severe and sustained alterations in gait, accompanied by an altered transcriptional landscape in distal musculoskeletal tissues, with marked reductions in bone and tendon growth and smaller, fibrotic hindlimb musculature. Sciatic nerve resection impaired cumulative growth in the Achilles tendon, shifting cell proliferation and matrix-driven growth trajectories and altering mechanotransduction gene programs toward inflammation and matrix catabolism with age. This work highlights the essential role of mechanical loading in driving mechanosignaling and postnatal growth trajectories in musculoskeletal tissues of the developing limb, with implications for overall musculoskeletal health in adulthood.
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BibTeX
@misc{johnson2026impaired,
title = {{Impaired loading following denervation elicits dynamic, differential growth trajectories of musculoskeletal tissues}},
author = {Talayah Johnson and Natalie L. Fogarty and Grey Hallstrom and Destiny Miller and Madison Dennis and Alisia Lin and Xi Jiang and Jiaqi Xiang and Joel D. Boerckel and Eiki Koyama and Lin Han and Josh R. Baxter and Robert L. Mauck and Nathaniel A. Dyment},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.26.761680},
url = {https://www.biorxiv.org/content/10.64898/2026.10.26.761680v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Impaired loading following denervation elicits dynamic, differential growth trajectories of musculoskeletal tissues
AU - Talayah Johnson
AU - Natalie L. Fogarty
AU - Grey Hallstrom
AU - Destiny Miller
AU - Madison Dennis
AU - Alisia Lin
AU - Xi Jiang
AU - Jiaqi Xiang
AU - Joel D. Boerckel
AU - Eiki Koyama
AU - Lin Han
AU - Josh R. Baxter
AU - Robert L. Mauck
AU - Nathaniel A. Dyment
PY - 2026
DA - 2026/10/26
PB - bioRxiv
DO - 10.64898/2026.10.26.761680
UR - https://www.biorxiv.org/content/10.64898/2026.10.26.761680v1
AB - Physical forces dictate the function and maintenance of adult musculoskeletal tissues. Yet, the impact of biophysical cues on the growth and maturation of these tissues, especially dense connective tissues, remains unclear. Here, we investigated the effects of neonatal mechanical loading on early postnatal growth of the musculoskeletal tissues of the lower limb, with particular focus on the Achilles tendon. We performed sciatic nerve resection (SNR) on one-day-old mice to denervate the hamstrings and distal hindlimb muscles. Sciatic Nerve Resection resulted in severe and sustained alterations in gait, accompanied by an altered transcriptional landscape in distal musculoskeletal tissues, with marked reductions in bone and tendon growth and smaller, fibrotic hindlimb musculature. Sciatic nerve resection impaired cumulative growth in the Achilles tendon, shifting cell proliferation and matrix-driven growth trajectories and altering mechanotransduction gene programs toward inflammation and matrix catabolism with age. This work highlights the essential role of mechanical loading in driving mechanosignaling and postnatal growth trajectories in musculoskeletal tissues of the developing limb, with implications for overall musculoskeletal health in adulthood.
SN - 2692-8205
ER -