Reduction in postnatal weight‐bearing does not alter the trajectory of murine meniscus growth and maturation

Abstract

The early post‐natal period represents a critical window for the maturation and development of orthopedic tissues, including those within the knee joint. To understand how mechanical loading impacts the maturational trajectory of the meniscus and other tissues of the hindlimb, perturbation of post‐natal weight bearing was achieved through surgical resection of the sciatic nerve in neonatal mice at 1 or 14 days old. Sciatic nerve resection (SNR) produced significant and persistent disruptions in gait, leading to reduced tibial length and reductions in Achilles tendon mechanical properties. However, SNR resulted in minimal disruptions in morphometric parameters of the menisci and other structures in the knee joint, with no differences in Col1a1‐YFP or Col2a1‐CFP expressing cells within the menisci. Furthermore, micromechanical properties of the meniscus and cartilage (as assessed by atomic force microscopy‐based nanoindentation testing) were not different between experimental groups. In contrast to our initial hypothesis, reduced hindlimb weight bearing via neonatal SNR did not significantly impact the growth and development of the knee meniscus. This unexpected finding demonstrates that the input mechanical threshold required to sustain meniscus development may be lower than previously hypothesized, though future studies incorporating skeletal kinematic models coupled with force plate measurements will be required to calculate the loads passing through the affected hindlimb and precisely define these thresholds. Collectively, these results provide insight into the mechanobiological responses of the meniscus to alterations in load, and contribute to our understanding of the factors that influence normal post‐natal development.This article is protected by copyright. All rights reserved.

Structure-Mechanics Principles and Mechanobiology of Fibrocartilage Pericellular Matrix: A Pivotal Role of Type V Collagen

“…This may represent an adaptive biological process for meniscal cells to maintain normal homeostasis under extensive physiological loadings. For example, following sciatic nerve resection surgery, murine meniscus was found to undergo normal postnatal growth despite substantial disruptions in joint loading and gaits [67]. Also, in other tissues, collagen V plays direct biological roles such as maintaining the muscle satellite stem cell niche through the Notch-Col V-Calcr axis [68], influencing fibroblast growth factor-2 (FGF-2)-mediated angiogenesis [69], as well as mediating cardiac and dermal wound healing by impacting integrin expression [70][71][72] and transforming growth factor-β (TGF-β) signaling in fibroblasts [73].…”