ArticleDevelopment (Cambridge, England)2009
Conditional inactivation of Has2 reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb.
Article in Development (Cambridge, England), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 148 citations in OpenAlex.
- Epigenetic regulation of vertebrate limb development: from field specification to tissue morphogenesis.Epigenetics · 2026Review
- Cartilage-SpecificBiomedicines · 2026Article
- Layilin at the crossroads of immunity and motility: a C-type lectin receptor in Hyaluronan Signaling.Glycobiology · 2025Review
- Fibroblast Has2 limits acute heart failure following myocardial infarction in male mice.Physiological reports · 2025Article
- Glycocalyx-targeted therapy prevents age-related muscle loss and declines in maximal exercise capacity.Aging · 2025Article
- Synovial joint cavitation during limb skeletogenesis entails Na/K-ATPase ion pump expression and osmoregulatory activity.Development (Cambridge, England) · 2025Article
- Hyaluronic Acid in Female Reproductive Health: Tailoring Molecular Weight to Clinical Needs in Obstetric and Gynecological Fields.Pharmaceutics · 2025Review
- Genetic Deficiency of Hyaluronan Synthase 2 in the Developing Limb Mesenchyme Impairs Postnatal Synovial Joint Formation.Biomedicines · 2025Article
- Activated cardiac fibroblasts are a primary source of high-molecular-weight hyaluronan production.American journal of physiology. Cell physiology · 2025Article
- High molecular weight hyaluronic acid alleviates ovariectomy-induced bone loss in mice.BMC musculoskeletal disorders · 2024Article
- Bone quality relies on hyaluronan synthesis - Insights from mice with complete knockout of hyaluronan synthase expression.Matrix biology plus · 2024Article
- Suppression of apoptosis impairs phalangeal joint formation in the pathogenesis of brachydactyly type A1.Nature communications · 2024Article
- Protecting the regenerative environment: selecting the optimal delivery vehicle for cartilage repair-a narrative review.Frontiers in bioengineering and biotechnology · 2024Review
- Advanced bioactive glue tethering Lubricin/PRG4 to promote integrated healing of avascular meniscus tears.Bioactive materials · 2023Article
- Article
- Downregulation of HAS‑2 regulates the chondrocyte cytoskeleton and induces cartilage degeneration by activating the RhoA/ROCK signaling pathway.International journal of molecular medicine · 2023Article
- Aggrecan and Hyaluronan: The Infamous Cartilage Polyelectrolytes - Then and Now.Advances in experimental medicine and biology · 2023Article
- Anti-Inflammatory Effects of the 35kDa Hyaluronic Acid Fragment (B-HA/HA35).Journal of inflammation research · 2023Article
- Hyaluronan Modulates the Biomechanical Properties of the Cornea.Investigative ophthalmology & visual science · 2022Article
- The hyaluronan-related genes HAS2, HYAL1-4, PH20 and HYALP1 are associated with prognosis, cell viability and spheroid formation capacity in ovarian cancer.Journal of cancer research and clinical oncology · 2022Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The glycosaminoglycan hyaluronan (HA) is a structural component of extracellular matrices and also interacts with cell surface receptors to directly influence cell behavior. To explore functions of HA in limb skeletal development, we conditionally inactivated the gene for HA synthase 2, Has2, in limb bud mesoderm using mice that harbor a floxed allele of Has2 and mice carrying a limb mesoderm-specific Prx1-Cre transgene. The skeletal elements of Has2-deficient limbs are severely shortened, indicating that HA is essential for normal longitudinal growth of all limb skeletal elements. Proximal phalanges are duplicated in Has2 mutant limbs indicating an involvement of HA in patterning specific portions of the digits. The growth plates of Has2-deficient skeletal elements are severely abnormal and disorganized, with a decrease in the deposition of aggrecan in the matrix and a disruption in normal columnar cellular relationships. Furthermore, there is a striking reduction in the number of hypertrophic chondrocytes and in the expression domains of markers of hypertrophic differentiation in the mutant growth plates, indicating that HA is necessary for the normal progression of chondrocyte maturation. In addition, secondary ossification centers do not form in the central regions of Has2 mutant growth plates owing to a failure of hypertrophic differentiation. In addition to skeletal defects, the formation of synovial joint cavities is defective in Has2-deficient limbs. Taken together, our results demonstrate that HA has a crucial role in skeletal growth, patterning, chondrocyte maturation and synovial joint formation in the developing limb.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.