Enhanced cartilage repair in ‘healer’ mice—New leads in the search for better clinical options for cartilage repair

Fitzgerald, Jamie

doi:10.1016/j.semcdb.2016.04.018

Cited by 15 publications

(15 citation statements)

References 94 publications

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“…When considering the use of animal models, it is important to note genetic and/or anatomical differences in animals compared to humans [ 102 , 103 , 104 , 105 , 106 ]. The injury models discussed here have been performed on mice, rats and rabbits.…”

Section: Results Of the In Vivo Ex Vivo And In Vitro Models That mentioning

confidence: 99%

An Evidence-Based Systematic Review of Human Knee Post-Traumatic Osteoarthritis (PTOA): Timeline of Clinical Presentation and Disease Markers, Comparison of Knee Joint PTOA Models and Early Disease Implications

Khella

Asgarian

Horvath

et al. 2021

IJMS

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Understanding the causality of the post-traumatic osteoarthritis (PTOA) disease process of the knee joint is important for diagnosing early disease and developing new and effective preventions or treatments. The aim of this review was to provide detailed clinical data on inflammatory and other biomarkers obtained from patients after acute knee trauma in order to (i) present a timeline of events that occur in the acute, subacute, and chronic post-traumatic phases and in PTOA, and (ii) to identify key factors present in the synovial fluid, serum/plasma and urine, leading to PTOA of the knee in 23–50% of individuals who had acute knee trauma. In this context, we additionally discuss methods of simulating knee trauma and inflammation in in vivo, ex vivo articular cartilage explant and in vitro chondrocyte models, and answer whether these models are representative of the clinical inflammatory stages following knee trauma. Moreover, we compare the pro-inflammatory cytokine concentrations used in such models and demonstrate that, compared to concentrations in the synovial fluid after knee trauma, they are exceedingly high. We then used the Bradford Hill Framework to present evidence that TNF-α and IL-6 cytokines are causal factors, while IL-1β and IL-17 are credible factors in inducing knee PTOA disease progresssion. Lastly, we discuss beneficial infrastructure for future studies to dissect the role of local vs. systemic inflammation in PTOA progression with an emphasis on early disease.

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Section: Results Of the In Vivo Ex Vivo And In Vitro Models That mentioning

confidence: 99%

An Evidence-Based Systematic Review of Human Knee Post-Traumatic Osteoarthritis (PTOA): Timeline of Clinical Presentation and Disease Markers, Comparison of Knee Joint PTOA Models and Early Disease Implications

Khella

Asgarian

Horvath

et al. 2021

IJMS

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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).…”

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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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“…As outlined by Fitzgerald [49] , adult articular cartilage has a poor capacity to undergo intrinsic repair, and despite an array of potential strategies developed to hasten intrinsic cartilage repair, strategies for fostering repair of large cartilage defects remain unsatisfactory. To restore cartilage with the same resistance to biomechanical loading as authentic articular cartilage that does not degrade over time, possible approaches applied in light of the complex osteoarthritic process that involves enzymatic degradation, pain, joint swelling, cartilage fragmentation, or softening, are care to protect an osteoarthritic joint from excess impact, while not favoring complete immobilization.…”

Section: Discussionmentioning

confidence: 99%

“…Employed therapeutically as magnetic nanoparticles, these fields may also have the potential to foster better extrinsic control over tissue engineered structures in the context of cartilage regeneration strategies [48] . Other potential strategies identified as promising in the literature are efforts to identify cartilage regeneration promoting genes, increased efforts to explore the relationship between cartilage healing and protection from osteoarthritis after trauma, and modulation of inflammation by drugs, and/or Wnt pathway activators and inhibitors thought to be implicated in the context of cartilage repair [49] . See Table 1 for selected examples of the diverse approaches reported in the current literature, including ultrasound therapy, laser therapy, electrical muscle stimulation, exercise, passive motion, and microcurrent stimulation that all appear promising.…”

Section: Contemporary Observationsmentioning

confidence: 99%

Articular Cartilage Regeneration: An Update of Possible Treatment Approaches

Marks¹

2017

International Journal of Orthopaedics

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repair themes in the leading databases were examined. Specific emphasis was placed on a broad array of efforts and observations concerning articular cartilage and its repair. Articles of historic significance and more current strategies designed to foster cartilage repair were focused on, and reported in narrative form. Ideas extracted from the voluminous literature were those that answered one or more of the key questions driving this research. RESULTS: Numerous attempts have been made over time to foster cartilage repair, using a variety of approaches such as creating artificial cartilage, and transplanting stem cells into damaged cartilage to promote repair. Most current strategies are forged in laboratories and do not always account for the complex disease process, and the importance mechanical and inflammatory determinants play in the disease. However, manipulating biophysical, and biomechanical stimuli favorably is likely to hold promise for attenuating destruction of/or for fostering cartilage viability and repair, even in the presence of adverse osteoarthritic cartilage tissue changes. CONCLUSION: More work is needed to examine the key upstream determinants leading to articular cartilage destruction, and to enhancing the viability of the tissue. Employing carefully construed therapeutic strategies known to impact articular cartilage homeostasis safely and effectively can potentially preserve chondrocyte homeostasis, either alone or in conjunction with new technologies.

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Enhanced cartilage repair in ‘healer’ mice—New leads in the search for better clinical options for cartilage repair

Cited by 15 publications

References 94 publications

An Evidence-Based Systematic Review of Human Knee Post-Traumatic Osteoarthritis (PTOA): Timeline of Clinical Presentation and Disease Markers, Comparison of Knee Joint PTOA Models and Early Disease Implications

An Evidence-Based Systematic Review of Human Knee Post-Traumatic Osteoarthritis (PTOA): Timeline of Clinical Presentation and Disease Markers, Comparison of Knee Joint PTOA Models and Early Disease Implications

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

Articular Cartilage Regeneration: An Update of Possible Treatment Approaches

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