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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MDPI AG
2025-05-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Yingcui Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
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| institution | OA Journals |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-0acaa9f914b3470daab85cdce6455bdb2025-08-20T02:24:26ZengMDPI AGBiomedicines2227-90592025-05-01136132410.3390/biomedicines13061324Genetic Deficiency of Hyaluronan Synthase 2 in the Developing Limb Mesenchyme Impairs Postnatal Synovial Joint FormationYingcui Li0Alexander Tress1Peter Maye2Kemar Edwards3Asiona Findletar4Nathaniel A. Dyment5Yu Yamaguchi6David W. Rowe7Gengyun Le-Chan8Sunny S. K. Chan9Kevin W.-H. Lo10Department of Biology, College of Arts and Sciences, University of Hartford, 200 Bloomfield Avenue, West Hartford, CT 06117, USADepartment of Biology, College of Arts and Sciences, University of Hartford, 200 Bloomfield Avenue, West Hartford, CT 06117, USACenter for Regenerative Medicine and Skeletal Development, University of Connecticut Health Center, Farmington, CT 06032, USADepartment of Biology, College of Arts and Sciences, University of Hartford, 200 Bloomfield Avenue, West Hartford, CT 06117, USADepartment of Biology, College of Arts and Sciences, University of Hartford, 200 Bloomfield Avenue, West Hartford, CT 06117, USADepartment of Orthopedic Surgery, University of Pennsylvania, Philadelphia, PA 19104, USAHuman Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USACenter for Regenerative Medicine and Skeletal Development, University of Connecticut Health Center, Farmington, CT 06032, USADepartment of Biology, College of Arts and Sciences, University of Hartford, 200 Bloomfield Avenue, West Hartford, CT 06117, USADepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USADepartment of Medicine, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030, USAHyaluronan, 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.https://www.mdpi.com/2227-9059/13/6/1324synovial joint formationlimb developmentcartilage homeostasishyaluronanhyaluronan synthase 2 (<i>Has2</i>) |
| spellingShingle | 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 Genetic Deficiency of Hyaluronan Synthase 2 in the Developing Limb Mesenchyme Impairs Postnatal Synovial Joint Formation Biomedicines synovial joint formation limb development cartilage homeostasis hyaluronan hyaluronan synthase 2 (<i>Has2</i>) |
| title | Genetic Deficiency of Hyaluronan Synthase 2 in the Developing Limb Mesenchyme Impairs Postnatal Synovial Joint Formation |
| title_full | Genetic Deficiency of Hyaluronan Synthase 2 in the Developing Limb Mesenchyme Impairs Postnatal Synovial Joint Formation |
| title_fullStr | Genetic Deficiency of Hyaluronan Synthase 2 in the Developing Limb Mesenchyme Impairs Postnatal Synovial Joint Formation |
| title_full_unstemmed | Genetic Deficiency of Hyaluronan Synthase 2 in the Developing Limb Mesenchyme Impairs Postnatal Synovial Joint Formation |
| title_short | Genetic Deficiency of Hyaluronan Synthase 2 in the Developing Limb Mesenchyme Impairs Postnatal Synovial Joint Formation |
| title_sort | genetic deficiency of hyaluronan synthase 2 in the developing limb mesenchyme impairs postnatal synovial joint formation |
| topic | synovial joint formation limb development cartilage homeostasis hyaluronan hyaluronan synthase 2 (<i>Has2</i>) |
| url | https://www.mdpi.com/2227-9059/13/6/1324 |
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