ArticlePLoS genetics2014
Differential effects of collagen prolyl 3-hydroxylation on skeletal tissues.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Transcriptome meta-analysis reveals a dysregulation in extra cellular matrix and cell junction associated gene signatures during Dengue virus infection.Scientific reports · 2016Pooled it
- Prolyl-3-hydroxylase 1 is a central regulator of collagen post-translational modifications and the collagen biosynthetic network.The Journal of biological chemistry · 2026Article
- Update on the Genetics of Osteogenesis Imperfecta.Calcified tissue international · 2024Review
- Milder presentation of osteogenesis imperfecta type VIII due to compound heterozygosity for a predicted loss-of-function variant and novel missense variant inCold Spring Harbor molecular case studies · 2023Article
- An Update on Animal Models of Osteogenesis Imperfecta.Calcified tissue international · 2022Review
- Osteogenesis Imperfecta: Mechanisms and Signaling Pathways Connecting Classical and Rare OI Types.Endocrine reviews · 2022Review
- Exploring the cardiac ECM during fibrosis: A new era with next-gen proteomics.Frontiers in molecular biosciences · 2022Review
- Collagen transport and related pathways in Osteogenesis Imperfecta.Human genetics · 2021Review
- Cosmetic Syndrome Correction with Calcium Hydroxylapatite-Based Filler in Patients with Connective Tissue Dysplasia.Dermatology research and practice · 2021Article
- Substitution of murine type I collagen A1 3-hydroxylation site alters matrix structure but does not recapitulate osteogenesis imperfecta bone dysplasia.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
- Characterization of PPIB interaction in the P3H1 ternary complex and implications for its pathological mutations.Cellular and molecular life sciences : CMLS · 2019Article
- Cellular stress due to impairment of collagen prolyl hydroxylation complex is rescued by the chaperone 4-phenylbutyrate.Disease models & mechanisms · 2019Article
- Genetic analysis of osteogenesis imperfecta in the Palestinian population: molecular screening of 49 affected families.Molecular genetics & genomic medicine · 2018Article
- The genetic implication of scoliosis in osteogenesis imperfecta: a review.Journal of spine surgery (Hong Kong) · 2017Review
- Review
- Fkbp10 Deletion in Osteoblasts Leads to Qualitative Defects in Bone.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017Article
- P3h3-null and Sc65-null Mice Phenocopy the Collagen Lysine Under-hydroxylation and Cross-linking Abnormality of Ehlers-Danlos Syndrome Type VIA.The Journal of biological chemistry · 2017Article
- Bone involvement in adult patients affected with Ehlers-Danlos syndrome.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2016Article
- Systemic Control of Bone Homeostasis by FGF23 Signaling.Current molecular biology reports · 2016Article
- Restoration of the serum level of SERPINF1 does not correct the bone phenotype in Serpinf1 null mice.Molecular genetics and metabolism · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
Mutations in the genes encoding cartilage associated protein (CRTAP) and prolyl 3-hydroxylase 1 (P3H1 encoded by LEPRE1) were the first identified causes of recessive Osteogenesis Imperfecta (OI). These proteins, together with cyclophilin B (encoded by PPIB), form a complex that 3-hydroxylates a single proline residue on the α1(I) chain (Pro986) and has cis/trans isomerase (PPIase) activity essential for proper collagen folding. Recent data suggest that prolyl 3-hydroxylation of Pro986 is not required for the structural stability of collagen; however, the absence of this post-translational modification may disrupt protein-protein interactions integral for proper collagen folding and lead to collagen over-modification. P3H1 and CRTAP stabilize each other and absence of one results in degradation of the other. Hence, hypomorphic or loss of function mutations of either gene cause loss of the whole complex and its associated functions. The relative contribution of losing this complex's 3-hydroxylation versus PPIase and collagen chaperone activities to the phenotype of recessive OI is unknown. To distinguish between these functions, we generated knock-in mice carrying a single amino acid substitution in the catalytic site of P3h1 (Lepre1(H662A) ). This substitution abolished P3h1 activity but retained ability to form a complex with Crtap and thus the collagen chaperone function. Knock-in mice showed absence of prolyl 3-hydroxylation at Pro986 of the α1(I) and α1(II) collagen chains but no significant over-modification at other collagen residues. They were normal in appearance, had no growth defects and normal cartilage growth plate histology but showed decreased trabecular bone mass. This new mouse model recapitulates elements of the bone phenotype of OI but not the cartilage and growth phenotypes caused by loss of the prolyl 3-hydroxylation complex. Our observations suggest differential tissue consequences due to selective inactivation of P3H1 hydroxylase activity versus complete ablation of the prolyl 3-hydroxylation complex.
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Registered trials
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