| http://purl.uniprot.org/citations/35947192 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35947192 | http://www.w3.org/2000/01/rdf-schema#comment | "IntroductionOsteoblasts require substantial amounts of energy to synthesize the bone matrix and coordinate skeleton mineralization. This study analyzed the effects of mitochondrial dysfunction on bone formation, nano-organization of collagen and apatite, and the resultant mechanical function in mouse limbs.Materials and methodsLimb mesenchyme-specific Tfam knockout (Tfamf/f;Prx1-Cre: Tfam-cKO) mice were analyzed morphologically and histologically, and gene expressions in the limb bones were assessed by in situ hybridization, qPCR, and RNA sequencing (RNA-seq). Moreover, we analyzed the mitochondrial function of osteoblasts in Tfam-cKO mice using mitochondrial membrane potential assay and transmission electron microscopy (TEM). We investigated the pathogenesis of spontaneous bone fractures using immunohistochemical analysis, TEM, birefringence analyzer, microbeam X-ray diffractometer and nanoindentation.ResultsForelimbs in Tfam-cKO mice were significantly shortened from birth, and spontaneous fractures occurred after birth, resulting in severe limb deformities. Histological and RNA-seq analyses showed that bone hypoplasia with a decrease in matrix mineralization was apparent, and the expression of type I collagen and osteocalcin was decreased in osteoblasts of Tfam-cKO mice, although Runx2 expression was unchanged. Decreased type I collagen deposition and mineralization in the matrix of limb bones in Tfam-cKO mice were associated with marked mitochondrial dysfunction. Tfam-cKO mice bone showed a significantly lower Young's modulus and hardness due to poor apatite orientation which is resulted from decreased osteocalcin expression.ConclusionMice with limb mesenchyme-specific Tfam deletions exhibited spontaneous limb bone fractures, resulting in severe limb deformities. Bone fragility was caused by poor apatite orientation owing to impaired osteoblast differentiation and maturation."xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.org/dc/terms/identifier | "doi:10.1007/s00774-022-01354-2"xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/author | "Imai Y."xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/author | "Hasegawa T."xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/author | "Yoshioka H."xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/author | "Nakano T."xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/author | "Goto A."xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/author | "Ishimoto T."xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/author | "Akiyama H."xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/author | "Amizuka N."xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/author | "Komura S."xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/author | "Ozasa R."xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/author | "Kuramitsu N."xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/name | "J Bone Miner Metab"xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/pages | "839-852"xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/title | "Deletion of Tfam in Prx1-Cre expressing limb mesenchyme results in spontaneous bone fractures."xsd:string |
| http://purl.uniprot.org/citations/35947192 | http://purl.uniprot.org/core/volume | "40"xsd:string |
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| http://purl.uniprot.org/uniprot/#_D3Z0F3-mappedCitation-35947192 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35947192 |
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| http://purl.uniprot.org/uniprot/#_E0CZ12-mappedCitation-35947192 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35947192 |