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Published on: December 8, 2023
Neonatal Achilles Tendon Microstructure is Negatively Impacted by Decorin and Biglycan Knockdown After Injury and
Zakary M Beach1, Courtney A Nuss1, Stephanie N Weiss1
1McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA.
Insights
Decorin and biglycan are crucial for neonatal tendon development and maturation. Their absence impairs tendon structure and mechanics, highlighting their importance in tendon repair and growth.
Area of Science:
- Biomedical Engineering
- Developmental Biology
- Orthopedic Research
Background:
- Neonatal tendons exhibit enhanced healing, prompting research into developmental therapeutics.
- Decorin and biglycan are key proteoglycans in collagen fibrillogenesis for tendon development, maintenance, and repair.
- The specific roles of decorin and biglycan in early neonatal tendon development and healing remain largely unexplored.
Purpose of the Study:
- To investigate the impact of decorin and biglycan knockdown on Achilles tendon structure and mechanics during neonatal development.
- To assess the effects of decorin and biglycan knockdown on the recovery of tendon properties after neonatal injury.
Main Methods:
- Utilized an inducible, compound decorin/biglycan knockdown mouse model.
- Examined tendon structure and mechanical properties during neonatal development and after injury.
- Analyzed collagen fibril microstructure, including fibril diameter distribution.
Main Results:
- Knockdown of decorin and biglycan significantly reduced mechanical properties of neonatal tendons.
- Tendons exhibited an immature microstructure with a predominance of small-diameter collagen fibrils and a lack of larger ones.
- Developmental impairment and compromised healing responses were observed in the absence of these proteoglycans.
Conclusions:
- Decorin and biglycan are essential for normal tendon growth and maturation during the neonatal period.
- These proteoglycans play a critical role in establishing proper collagen fibril organization and mechanical integrity.
- Findings underscore the potential of targeting decorin and biglycan pathways for improving neonatal tendon injury therapeutics.
Abstract:
Interest in studying neonatal development and the improved healing response observed in neonates is increasing, with the goal of using this work to create better therapeutics for tendon injury. Decorin and biglycan are two small leucine-rich proteoglycans that play important roles in collagen fibrillogenesis to develop, maintain, and repair tendon structure. However, little is known about the roles of decorin and biglycan in early neonatal development and healing. The goal of this study was to determine the effects of decorin and biglycan knockdown on Achilles tendon structure and mechanics during neonatal development and recovery of these properties after injury of the neonatal tendon. We hypothesized that knockdown of decorin and biglycan would disrupt the neonatal tendon developmental process and produce tendons with impaired mechanical and structural properties. We found that knockdown of decorin and biglycan in an inducible, compound decorin/biglycan knockdown model, both during development and after injury, in neonatal mice produced tendons with reduced mechanical properties. Additionally, the collagen fibril microstructure resembled an immature tendon with a large population of small diameter fibrils and an absence of larger diameter fibrils. Overall, this study demonstrates the importance of decorin and biglycan in facilitating tendon growth and maturation during neonatal development.
