ArticleThe Journal of biological chemistry2015
Severe Extracellular Matrix Abnormalities and Chondrodysplasia in Mice Lacking Collagen Prolyl 4-Hydroxylase Isoenzyme II in Combination with a Reduced Amount of Isoenzyme I.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 79 citations in OpenAlex.
- Collagen Prolyl 4-Hydroxylase: An Emerging Key Player in Cardiac Fibrosis.Journal of cardiovascular translational research · 2026Review
- P4HA3 is dispensable for prolyl 4-hydroxylation of type I collagen during mouse development.The Journal of biological chemistry · 2026Article
- P4HA2 Participates in Pathogenesis of Refractive Error by Regulating Collagen Posttranslational Modification and Extracellular Matrix Balance.Human mutation · 2026Article
- Collagen IV biosynthesis: Intracellular choreography of post-translational modifications.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Comprehensive analysis of the effects ofFrontiers in cell and developmental biology · 2025Article
- ER-resident proteins are key players in cartilage and bone homeostasis.Frontiers in cell and developmental biology · 2025Review
- The new insight into the role of hydroxyproline in metabolism of cancer cells.Frontiers in cell and developmental biology · 2025Review
- Skeletal pathology in mouse models of Gould syndrome is partially alleviated by genetically reducing TGFβ signaling.Matrix biology : journal of the International Society for Matrix Biology · 2024Article
- Proteomic insights into the extracellular matrix: a focus on proteoforms and their implications in health and disease.Expert review of proteomics · 2024Review
- Profiling native pulmonary basement membrane stiffness using atomic force microscopy.Nature protocols · 2024Article
- Genome-wide association study for bone quality of ducks during the laying period.Poultry science · 2024Article
- GDF9Cell communication and signaling : CCS · 2024Article
- Article
- Cycloheximide promotes type I collagen maturation mainly via collagen prolyl 4-hydroxylase subunit α2.Acta biochimica et biophysica Sinica · 2022Article
- Reduced Bone Mass in Collagen Prolyl 4-HydroxylaseJBMR plus · 2022Article
- P4HA2-induced prolyl hydroxylation suppresses YAP1-mediated prostate cancer cell migration, invasion, and metastasis.Oncogene · 2021Article
- P4HA2 promotes cell proliferation and migration in glioblastoma.Oncology letters · 2021Article
- In-depth correlation analysis demonstrates that 4-hydroxyproline at the Yaa position of Gly-Xaa-Yaa repeats dominantly stabilizes collagen triple helix.Matrix biology plus · 2021Article
- Metabolic engineering strategy for synthetizing trans-4-hydroxy-L-proline in microorganisms.Microbial cell factories · 2021Review
- Roles of HIF and 2-Oxoglutarate-Dependent Dioxygenases in Controlling Gene Expression in Hypoxia.Cancers · 2021Review
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Authors and funding
16 authors at 4 institutions in 4 countries.
Funding
Abstract
Collagen prolyl 4-hydroxylases (C-P4H-I, C-P4H-II, and C-P4H-III) catalyze formation of 4-hydroxyproline residues required to form triple-helical collagen molecules. Vertebrate C-P4Hs are α2β2 tetramers differing in their catalytic α subunits. C-P4H-I is the major isoenzyme in most cells, and inactivation of its catalytic subunit (P4ha1(-/-)) leads to embryonic lethality in mouse, whereas P4ha1(+/-) mice have no abnormalities. To study the role of C-P4H-II, which predominates in chondrocytes, we generated P4ha2(-/-) mice. Surprisingly, they had no apparent phenotypic abnormalities. To assess possible functional complementarity, we established P4ha1(+/-);P4ha2(-/-) mice. They were smaller than their littermates, had moderate chondrodysplasia, and developed kyphosis. A transient inner cell death phenotype was detected in their developing growth plates. The columnar arrangement of proliferative chondrocytes was impaired, the amount of 4-hydroxyproline and the Tm of collagen II were reduced, and the extracellular matrix was softer in the growth plates of newborn P4ha1(+/-);P4ha2(-/-) mice. No signs of uncompensated ER stress were detected in the mutant growth plate chondrocytes. Some of these defects were also found in P4ha2(-/-) mice, although in a much milder form. Our data show that C-P4H-I can to a large extent compensate for the lack of C-P4H-II in proper endochondral bone development, but their combined partial and complete inactivation, respectively, leads to biomechanically impaired extracellular matrix, moderate chondrodysplasia, and kyphosis. Our mouse data suggest that inactivating mutations in human P4HA2 are not likely to lead to skeletal disorders, and a simultaneous decrease in P4HA1 function would most probably be required to generate such a disease phenotype.
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