A novel transgenic murine model with persistently brittle bones simulating osteogenesis imperfecta type I

Liu, Yi; Wang, Jianhai; Liu, Shuo; Kuang, Ming-jie; Jing, Yaqing; Zhao, Yijiao; Wang, Zihan; Li, Guang

doi:10.1016/j.bone.2019.07.021

Cited by 16 publications

(25 citation statements)

References 46 publications

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“…5 B–F ). ( 26 ) Stem cell infusion except the autologous ADSCs +/−365 significantly improved all bone biomechanical parameters (Fig. 5 B–F ).…”

Section: Resultsmentioning

confidence: 84%

“…( 43 ) A remarkable downregulation of YAP and downstream Runx2 transcription have been found in adipose‐derived mesenchymal stem cells (ADSCs) of our newly constructed OI type I mouse model ( Col1a1 +/−365 mice). ( 26 ) But the relationship between lowered YAP signaling and impaired osteogenic potential of the defective ADSCs with Col1a1 gene haploinsufficiency still remains to be illuminated.…”

Section: Discussionmentioning

confidence: 99%

“…The Col1a1 +/−365 mice with the same genetic background were propagated and identified according to methods described in our previous report. ( 26 ) Both types of mice were kept and handled under specific pathogen‐free (SPF) conditions in accordance with the approval by Animal Care and Use Committee of Tianjin Medical University (TMUaMEC 2017012). Only male mice were used in the present study.…”

Section: Methodsmentioning

confidence: 99%

“…Adipose‐derived mesenchymal stem cells (ADSCs) from 6‐week‐old male WT (ADSCs wt ) and Col1a1 +/−365 mice (ADSCs +/−365 ) were isolated as described previously. ( 26 ) Briefly, cells of adipose tissues near epididymis, groin, and underarm were digested using 0.2% type I collagenase (Sigma‐Aldrich, St. Louis, MO, USA) and adherently cultured in αMEM medium (Gibco, Thermo Fisher Scientific, Waltham, MA, USA) supplemented with 15% fetal bovine serum (FBS, Gibco) and 1% penicillin/streptomycin (PS, Gibco). The medium was replaced with fresh medium 4 days later.…”

Section: Methodsmentioning

confidence: 99%

“…( 25 ) Our previously published work also indicated that the weakened bone‐forming ability of adipose‐derived mesenchymal stem cells (ADSCs) from the newly constructed OI type I mouse model (heterozygous Col1a1 +/−365 mouse) was associated with YAP downregulation and nuclear localization decrease. ( 26 ) But the change of the upstream and downstream signal molecules caused by Col1a1 gene haploinsufficiency is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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Modification of COL1A1 in Autologous Adipose Tissue-Derived Progenitor Cells Rescues the Bone Phenotype in a Mouse Model of Osteogenesis Imperfecta

Liu

Wang

et al. 2020

Journal of Bone and Mineral Research

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Osteogenesis imperfecta (OI) is a congenital genetic disorder mainly manifested as bone fragility and recurrent fracture. Mutation of COL1A1/COL1A2 genes encoding the type I collagen are most responsible for the clinical patients. Allogenic mesenchymal stem cells (MSCs) provide the potential to treat OI through differentiation into osteoblasts. Autologous defective MSCs have not been utilized in OI treatment mainly because of their impaired osteogenesis, but the latent mechanism has not been well understood. Here, the relative signaling abnormality of adipose‐derived mesenchymal stem cells (ADSCs) isolated from OI type I mice (Col1a1+/−365 mice) was explored. Autologous ADSCs transfected by retrovirus carrying human COL1A1 gene was first utilized in OI therapy. The results showed that decreased activity of Yes‐associated protein (YAP) due to hyperactive upstream Hippo kinases greatly contributed to the weakened bone‐forming capacity of defective ADSCs. Recovered collagen synthesis of autologous ADSCs by COL1A1 gene modification normalized Hippo/YAP signaling and effectively rescued YAP‐mediated osteogenesis. And the COL1A1 gene engineered autologous ADSCs efficaciously improved the microstructure, enhanced the mechanical properties and promoted bone formation of Col1a1+/−365 mice after femoral bone marrow cavity delivery and might serve as an alternative source of stem cells in OI treatment. © 2021 American Society for Bone and Mineral Research (ASBMR).

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“…5 B–F ). ( 26 ) Stem cell infusion except the autologous ADSCs +/−365 significantly improved all bone biomechanical parameters (Fig. 5 B–F ).…”

Section: Resultsmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Modification of COL1A1 in Autologous Adipose Tissue-Derived Progenitor Cells Rescues the Bone Phenotype in a Mouse Model of Osteogenesis Imperfecta

Liu

Wang

et al. 2020

Journal of Bone and Mineral Research

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Curative Cell and Gene Therapy for Osteogenesis Imperfecta

Lee

O’Donohue

Ginn

et al. 2020

Journal of Bone and Mineral Research

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Osteogenesis imperfecta (OI) describes a series of genetic bone fragility disorders that can have a substantive impact on patient quality of life. The multidisciplinary approach to management of children and adults with OI primarily involves the administration of antiresorptive medication, allied health (physiotherapy and occupational therapy), and orthopedic surgery. However, advances in gene editing technology and gene therapy vectors bring with them the promise of gene-targeted interventions to provide an enduring or perhaps permanent cure for OI. This review describes emergent technologies for cell-and gene-targeted therapies, major hurdles to their implementation, and the prospects of their future success with a focus on bone disorders.

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Therapeutic approaches to activate the canonical Wnt pathway for bone regeneration

Nelson

Fontana

Miclau

et al. 2022

J Tissue Eng Regen Med

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Activation of the canonical Wingless‐related integration site (Wnt) pathway has been shown to increase bone formation and therefore has therapeutic potential for use in orthopedic conditions. However, attempts at developing an effective strategy to achieve Wnt activation has been met with several challenges. The inherent hydrophobicity of Wnt ligands makes isolating and purifying the protein difficult. To circumvent these challenges, many have sought to target extracellular inhibitors of the Wnt pathway, such as Wnt signaling pathway inhibitors Sclerostin and Dickkopf‐1, or to use small molecules, ions and proteins to increase target Wnt genes. Here, we review systemic and localized bioactive approaches to enhance bone formation or improve bone repair through antibody‐based therapeutics, synthetic Wnt surrogates and scaffold doping to target canonical Wnt. We conclude with a brief review of emerging technologies, such as mRNA therapy and Clustered Regularly Interspaced Short Palindromic Repeats technology, which serve as promising approaches for future clinical translation.

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A novel transgenic murine model with persistently brittle bones simulating osteogenesis imperfecta type I

Cited by 16 publications

References 46 publications

Modification of COL1A1 in Autologous Adipose Tissue-Derived Progenitor Cells Rescues the Bone Phenotype in a Mouse Model of Osteogenesis Imperfecta

Modification of COL1A1 in Autologous Adipose Tissue-Derived Progenitor Cells Rescues the Bone Phenotype in a Mouse Model of Osteogenesis Imperfecta

Curative Cell and Gene Therapy for Osteogenesis Imperfecta

Therapeutic approaches to activate the canonical Wnt pathway for bone regeneration

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