Genetic Deficiency of Hyaluronan Synthase 2 in the Developing Limb Mesenchyme Impairs Postnatal Synovial Joint Formation

Hyaluronan, a key component of the extracellular matrix, plays a crucial role in joint development and maintenance. In order to determine the role of hyaluronan function in joint development and homeostasis, conditional loss-of-function experiments of Hyaluronan Synthase 2 (<i>Has2</i>)...

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Main Authors: Yingcui Li, Alexander Tress, Peter Maye, Kemar Edwards, Asiona Findletar, Nathaniel A. Dyment, Yu Yamaguchi, David W. Rowe, Gengyun Le-Chan, Sunny S. K. Chan, Kevin W.-H. Lo
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/6/1324
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Summary:Hyaluronan, a key component of the extracellular matrix, plays a crucial role in joint development and maintenance. In order to determine the role of hyaluronan function in joint development and homeostasis, conditional loss-of-function experiments of Hyaluronan Synthase 2 (<i>Has2</i>) were carried out in mice. <i>Has2</i> depletion in limb mesenchymal cells led to severely shortened limbs with appendicular joints that are deformed, decreased proteoglycan content as characterized by Safranin-O staining, and severely pitted epiphyseal ends of long bones and deformed joints as viewed by micro-CT reconstructions. The embryonic deletion of <i>Has2</i> in mesoderm mesenchyme of limbs by Prx1-Cre confirmed its involvement in joint development, while in situ hybridization and hyaluronan staining confirmed <i>Has2</i> expression and abundant accumulation of hyaluronan in the onset of joint formation, the joint interzone. These findings position <i>Has2</i> as the main hyaluronan-making enzyme in articular cartilage and highlight its essential function in joint formation and retention of proteoglycans of the extracellular matrix of the cartilage.
ISSN:2227-9059