Mechanical forces imposed through isotonic muscle contractions are essential for proper tendon growth. Processes that inhibit or hinder this contraction disrupt this mechanical loading, leading to tendonitis, tendinosis, or tendon ruptures. Because the sciatic nerve innervates the calf muscles that load the Achilles' tendon, we used sciatic nerve resection (SNR) to unload the distal limb in our study.

This study aims to understand the role of mechanical forces on the tendon tissue; however, the meniscus serves as a related connective tissue for analysis, as it also derives from mesenchymal progenitors and is composed primarily of Type I collagen. While prior studies in adult tendons have shown that altered loading changes tissue morphology and mechanical properties, research on the meniscus has found that reduced postnatal weight-bearing does not affect its growth or maturation. These contrasting findings prompted us to investigate how mechanical forces influence early tendon development. We performed unilateral SNR on neonatal mice at postnatal day 1 (P1) and analyzed gait at P14, P42, and P56, as well as tendon growth histologically at all time points.

SNR limbs displayed sustained gait abnormalities, including reduced toe spread, increased dorsiflexion, and decreased ankle height at toe-off, indicating diminished push-off strength and muscle force generation. Achilles' tendon cross-sectional area was significantly reduced at all timepoints, and although SNR tendons exhibited a late growth surge between P42 and P56, their overall trajectory was altered. Hamstring analysis revealed increased hip abduction, reflecting compensatory gait changes despite preserved hamstring and quadriceps activity.

Our findings show early unloading through SNR impairs tendon growth, disrupts normal gait mechanics, and compromises muscle function. Our results underscore the critical role of mechanical forces in postnatal tendon development. Future work involves understanding the molecular basis of our findings through bulk RNA sequencing and gene expression analysis for maturation gradients in clonal arrays, using Xenium to further elucidate how tendons grow.