Superior angiogenesis facilitates digit regrowth in MRL/MpJ mice compared to C57BL/6 mice

Kwiatkowski, Alex; Piatkowski, Mark; Miao, Chen; Kan, Lijuan; Meng, Qingshu; Fan, Huimin; Osman, Abdel‐Hamid K.; Liu, Zhongmin; Ledford, Benjamin T.; He, Jia‐Qiang

doi:10.1016/j.bbrc.2016.03.149

Cited by 12 publications

(11 citation statements)

References 26 publications

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“…5,15,53 As expected, our results indicate that MRL/MpJ mice show more callus mineralization, and the regenerated bone returns to normal bone structure faster than the control strains despite the fact that callus size is not larger than control mice. 5,15,53 As expected, our results indicate that MRL/MpJ mice show more callus mineralization, and the regenerated bone returns to normal bone structure faster than the control strains despite the fact that callus size is not larger than control mice.…”

Section: Discussionsupporting

confidence: 83%

High bone microarchitecture, strength, and resistance to bone loss in MRL/MpJ mice correlates with activation of different signaling pathways and systemic factors

et al. 2019

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Abbreviations: ANOVA, analysis of variance; Adcy4, adenylate cyclase 4; Atp1b3, beta 3 polypeptide; BMMs, bone marrow macrophages; BMPs, bone morphogenetic proteins; BV, bone volume ; SLE, systemic lupus erythematosus; BV/TV, Bone volume/total volume; Capn1, calpain 1; CatK, Cathepsin K; cDNA, complementary deoxyribonucleic acid; DAB, diaminobenzidine; EDTA, Ethylenediaminetetraacetic acid; ELISA, enzyme-linked immunosorbent assay; Grin2a, glutamate receptor, ionotropic, NMDA2A (epsilon 1); GH, growth hormone; H1F1α, hypoxia inducible factor 1 α; IGF1, insulin-like growth factor 1; Itgb1, integrin beta 1; KEGG, Kyoto Encyclopedia of Genes and Genomes; LC-MS, liquid chromatography and mass spectrometry; M-CSF, macrophage cloning stimulating factor; microCT, micro-computed tomography; MAR, mineral apposition rate; α-MEM, Minimum Essential Medium Eagle -Alpha Modification; Nfatc1, nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1(Nfatc1); NTX-1, N-terminal telopeptides of type-1 collagen; OB, osteoblasts; OC, osteoclasts; OPG, osteoprotegerin; pAKT, protein kinase B; Pik3r2, phosphatidylinositol 3-kinase, regulatory subunit, and polypeptide 2 (p85 beta); PBS, phosphate buffer; PCNA, proliferation cell nuclear antigen; Ppp1r12b, protein phosphatase 1, regulatory (inhibitor) subunit 12B; pSMAD5, phosphorylated mothers against decapentaplegic homolog 5; p38MAPK, P38 mitogen-activated protein kinases; P1NP, Cross-linked C-telopeptide of type 1 collagen; PXN, paxillin; qPCR, quantitative polymerase chain reaction; RANKL, Receptor activator of nuclear factor kappa-Β ligand; Rac2, RAS-related C3 botulinum substrate 2; RNA, ribonucleic acid; SD, standard deviation; Sos1, son of sevenless homolog 1; Tb.N, trabecular number; Tb.Th, trabecular thickness; Tb.Sp, trabecular separation; TRAP, tartrate-resistant acid phosphatase; Ult Load, ultimate load force. Correspondence AbstractThe MRL/MpJ mice have demonstrated an enhanced tissue regeneration capacity for various tissues. In the present study, we systematically characterized bone microarchitecture and found that MRL/MpJ mice exhibit higher bone microarchitecture and strength compared to both C57BL/10J and C57BL/6J WT mice at 2, 4, and 10 months of age. The higher bone mass in MRL/MpJ mice was correlated to increased osteoblasts, decreased osteoclasts, higher cell proliferation, and bone formation, and enhanced pSMAD5 signaling earlier during postnatal development (2-month old) in the spine trabecular bone, and lower bone resorption rate at later age. Furthermore, these mice exhibit accelerated fracture healing via enhanced pSMAD5, pAKT and p-P38MAPK pathways compared to control groups. Moreover, MRL/MpJ mice demonstrated resistance to ovariectomy-induced bone loss as evidenced by maintaining higher bone volume/tissue volume (BV/TV) and lower percentage of bone loss later after ovariectomy. The consistently higher serum IGF1 level and lower RANKL 790 | SUN et al.

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Section: Discussionsupporting

confidence: 83%

High bone microarchitecture, strength, and resistance to bone loss in MRL/MpJ mice correlates with activation of different signaling pathways and systemic factors

et al. 2019

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“…Thus, for the first time, our results reveal discrepancies between mice and human fingertip regeneration. However, in a recent study, regenerated fingertips in fast-healing mice showed 70% increased vascularization compared to non-healing mice with impaired regeneration [30]. These data along with our observations, suggest an important role for higher blood flow in the fingertip regeneration in mammalians.…”

Section: Discussionsupporting

confidence: 77%

First Insights into Human Fingertip Regeneration by Echo-Doppler Imaging and Wound Microenvironment Assessment

Jafari

Müller

Grognuz

et al. 2017

IJMS

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Fingertip response to trauma represents a fascinating example of tissue regeneration. Regeneration derives from proliferative mesenchymal cells (blastema) that subsequently differentiate into soft and skeletal tissues. Clinically, conservative treatment of the amputated fingertip under occlusive dressing can shift the response to tissue loss from a wound repair process towards regeneration. When analyzing by Immunoassay the wound exudate from occlusive dressings, the concentrations of brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) were higher in fingertip exudates than in burn wounds (used as controls for wound repair versus regeneration). Vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor (PDGF) were highly expressed in both samples in comparable levels. In our study, pro-inflammatory cytokines were relatively higher expressed in regenerative fingertips than in the burn wound exudates while chemokines were present in lower levels. Functional, vascular and mechanical properties of the regenerated fingertips were analyzed three months after trauma and the data were compared to the corresponding fingertip on the collateral uninjured side. While sensory recovery and morphology (pulp thickness and texture) were similar to uninjured sides, mechanical parameters (elasticity, vascularization) were increased in the regenerated fingertips. Further studies should be done to clarify the importance of inflammatory cells, immunity and growth factors in determining the outcome of the regenerative process and its influence on the clinical outcome.

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“…Murphy Roths Large (MRL/MpJ) mice, also known as super healer mice, have the ability to remarkably repair a variety of musculoskeletal tissue injuries throughout their lifespan, including ear wounds, bone lesions, and articular cartilage lesions (1)(2)(3). A previous study has linked the superior healing capacity of MRL/MpJ mice to various processes, including decreased scar tissue formation, modified inflammatory reactions, reduced cell apoptosis, increased cell proliferation and differentiation, improved remodeling, and enhanced stem cell function (4).…”

mentioning

confidence: 99%

Hypoxia‐inducible factor 1α (HIF‐1α) is a major determinant in the enhanced function of muscle‐derived progenitors from MRL/MpJ mice

et al. 2019

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Although the mouse strain Murphy Roths Large (MRL/MpJ) possesses high regenerative potential, the mechanism of tissue regeneration, including skeletal muscle, in MRL/MpJ mice after injury is still unclear. Our previous studies have shown that muscle‐derived stem/progenitor cell (MDSPC) function is significantly enhanced in MRL/MpJ mice when compared with MDSPCs isolated from age‐matched wild‐type (WT) mice. Using mass spectrometry–based proteomic analysis, we identified increased expression of hypoxia‐inducible factor (HIF) 1α target genes (expression of glycolytic factors and antioxidants) in sera from MRL/MpJ mice compared with WT mice. Therefore, we hypothesized that HIF‐1α promotes the high muscle healing capacity of MRL/MpJ mice by increasing the potency of MDSPCs. We demonstrated that treating MRL/MpJ MDSPCs with dimethyloxalylglycine and CoCl2 increased the expression of HIF‐1α and target genes, including angiogenic and cell survival genes. We also observed that HIF‐1α activated the expression of paired box (Pax)7 through direct interaction with the Pax7 promoter. Furthermore, we also observed a higher myogenic potential of MDSPCs derived from prolyl hydroxylase (Phd) 3—knockout (Phd3−/−) mice, which displayed higher stability of HIF‐1α. Taken together, our findings suggest that HIF‐1α is a major determinant in the increased MDSPC function of MRL/MpJ mice through enhancement of cell survival, proliferation, and myogenic differentiation.—Sinha, K. M., Tseng, C., Guo, P., Lu, A., Pan, H., Gao, X., Andrews, R., Eltzschig, H., Huard, J. Hypoxia‐inducible factor 1α (HIF‐1α) is a major determinant in the enhanced function of muscle‐derived progenitors from MRL/MpJ mice. FASEB J. 33, 8321–8334 (2019). http://www.fasebj.org

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Superior angiogenesis facilitates digit regrowth in MRL/MpJ mice compared to C57BL/6 mice

Cited by 12 publications

References 26 publications

High bone microarchitecture, strength, and resistance to bone loss in MRL/MpJ mice correlates with activation of different signaling pathways and systemic factors

High bone microarchitecture, strength, and resistance to bone loss in MRL/MpJ mice correlates with activation of different signaling pathways and systemic factors

First Insights into Human Fingertip Regeneration by Echo-Doppler Imaging and Wound Microenvironment Assessment

Hypoxia‐inducible factor 1α (HIF‐1α) is a major determinant in the enhanced function of muscle‐derived progenitors from MRL/MpJ mice

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