ArticleDevelopmental biology2014
Loss of VHL in mesenchymal progenitors of the limb bud alters multiple steps of endochondral bone development.
Article in Developmental biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- "Quiescence" in the resting zone of the growth plate: a systematic review.Stem cells (Dayton, Ohio) · 2026Pooled it
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- HIF1 activation safeguards cortical bone formation against impaired oxidative phosphorylation.JCI insight · 2024Article
- Unveiling the role of hypoxia-inducible factor 2alpha in osteoporosis: Implications for bone health.World journal of stem cells · 2024Article
- Article
- Genome-wide CRISPR screening of chondrocyte maturation newly implicates genes in skeletal growth and height-associated GWAS loci.Cell genomics · 2023Article
- Iron Deficiency and Iron Deficiency Anemia: Potential Risk Factors in Bone Loss.International journal of molecular sciences · 2023Review
- Hypoxia-Inducible Factor-2α Signaling in the Skeletal System.JBMR plus · 2023Review
- Degradation-Resistant Hypoxia Inducible Factor-2α in Murine Osteocytes Promotes a High Bone Mass Phenotype.JBMR plus · 2023Article
- Epidermal growth factor signalling pathway in endochondral ossification: an evidence-based narrative review.Annals of medicine · 2022Review
- Review
- Hnrnpk maintains chondrocytes survival and function during growth plate development via regulating Hif1α-glycolysis axis.Cell death & disease · 2022Article
- Deletion ofFrontiers in immunology · 2022Article
- Testing Hypoxia in Pig Meniscal Culture: Biological Role of the Vascular-Related Factors in the Differentiation and Viability of Neonatal Meniscus.International journal of molecular sciences · 2021Article
- Hypoxia as a Stimulus for the Maturation of Meniscal Cells: Highway to Novel Tissue Engineering Strategies?International journal of molecular sciences · 2021Article
- Fetal Growth Plate Cartilage : Histological and Immunohistochemical Techniques.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Hypoxia Inducible Factor-1α in Osteochondral Tissue Engineering.Tissue engineering. Part B, Reviews · 2020Review
- Suppressing Mitochondrial Respiration Is Critical for Hypoxia Tolerance in the Fetal Growth Plate.Developmental cell · 2019Article
- Hypoxia Signaling in the Skeleton: Implications for Bone Health.Current osteoporosis reports · 2019Review
- Analysis of Mouse Growth Plate Development.Current protocols in mouse biology · 2016Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Adaptation to low oxygen tension (hypoxia) is a critical event during development. The transcription factors Hypoxia Inducible Factor-1α (HIF-1α) and HIF-2α are essential mediators of the homeostatic responses that allow hypoxic cells to survive and differentiate. Von Hippel-Lindau protein (VHL) is the E3 ubiquitin ligase that targets HIFs to the proteasome for degradation in normoxia. We have previously demonstrated that the transcription factor HIF-1α is essential for survival and differentiation of growth plate chondrocytes, whereas HIF-2α is not necessary for fetal growth plate development. We have also shown that VHL is important for endochondral bone development, since loss of VHL in chondrocytes causes severe dwarfism. In this study, in order to expand our understanding of the role of VHL in chondrogenesis, we conditionally deleted VHL in mesenchymal progenitors of the limb bud, i.e. in cells not yet committed to the chondrocyte lineage. Deficiency of VHL in limb bud mesenchyme does not alter the timely differentiation of mesenchymal cells into chondrocytes. However, it causes structural collapse of the cartilaginous growth plate as a result of impaired proliferation, delayed terminal differentiation, and ectopic death of chondrocytes. This phenotype is associated to delayed replacement of cartilage by bone. Notably, loss of HIF-2α fully rescues the late formation of the bone marrow cavity in VHL mutant mice, though it does not affect any other detectable abnormality of the VHL mutant growth plates. Our findings demonstrate that VHL regulates bone morphogenesis as its loss considerably alters size, shape and overall development of the skeletal elements.
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Registered trials
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.