Mouse Models in Bone Fracture Healing Research

Haffner‐Luntzer, Melanie; Kovtun, Anna; Rapp, Anna E.; Ignatius, Anita

doi:10.1007/s40610-016-0037-3

Cited by 55 publications

(50 citation statements)

References 116 publications

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“…These can result from implant anchorage problems in the fragile bone and/or from the disturbed healing capacity of the bone tissue itself . There is need for suitable animal models to test newly developed implants and biomaterials on the one hand and on the other hand to better understand the poor bone healing capacity and delayed fracture healing on a cellular and molecular level . Generally, animal models to investigate the osteoporotic fracture healing process should reflect the clinical scenario of bone loss, for example, postmenopausal, senile, or secondary osteoporosis.…”

Section: Comorbidities Influencing Fracture Healingmentioning

confidence: 99%

“…Over the last two decades, the mouse became the most frequently used animal model in biomedical research due to easy handling, low husbandry costs, a short reproductive cycle, availability of transgenic mice and of specific analytic tools, including monoclonal antibodies against a broad variety of antigens to target individual molecules in vivo . In addition, the mouse genome contents a very high number of orthologs and homologs to human genes, making the mouse a valuable model organism for bone research, although the bone structure and the bone remodelling process differs significantly from humans . Because of the latter facts, there is also an increasing interest in non‐rodent translational models due to approximate human size, similar secondary bone structure, similarities in pathophysiology and the possibility to translate knowledge from “bench‐to‐bedside” …”

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confidence: 99%

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Review of Animal Models of Comorbidities in Fracture‐Healing Research

Haffner‐Luntzer¹,

Hankenson

Ignatius³

et al. 2019

Journal Orthopaedic Research

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There is clinical evidence that patient-specific comorbidities like osteoporosis, concomitant tissue injury, and ischemia may strongly interfere with bone regeneration. However, underlying mechanisms are still unclear. To study these mechanisms in detail, appropriate animal models are needed. For decades, bone healing has been studied in large animals, including dogs, rabbits, pigs, or sheep. However, large animal models display a limited ability to study molecular pathways and cellular functions. Therefore in recent years, mice and rats have become increasingly popular as a model organism for fracture healing research due to the availability of molecular analysis tools and transgenic models. Both large and small animals can be used to study comorbidities and risk factors, modelling the human clinical situation. However, attention has to be paid when choosing an appropriate model due to species differences between large animals, rodents, and humans. This review focuses on large and small animal models for the common comorbidities ischemic injury/reduced vascularization, osteoporosis, and polytrauma, and critically discusses the translational and molecular aspects of these models. Here, we review material which was presented at the workshop "Animal

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Section: Comorbidities Influencing Fracture Healingmentioning

confidence: 99%

mentioning

confidence: 99%

Review of Animal Models of Comorbidities in Fracture‐Healing Research

Haffner‐Luntzer¹,

Hankenson

Ignatius³

et al. 2019

Journal Orthopaedic Research

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“…Thus, not all the studies performed had sufficient power to compare sex as a variable, though we did not observe sexually dimorphic behavior for any outcome measure, and our prior assessment of YAP/TAZ regulation of bone development did not show an effect of sex (16) . Second, we used an open fracture model, which may affect the kinetics and immunology of the fracture repair process (73,74) . We initially began these experiments using a closed fracture model, following the Einhorn method (75) , but this produced a high percentage of comminuted fractures in the YAP/TAZ cKO groups.…”

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confidence: 99%

YAP and TAZ promote periosteal osteoblast precursor expansion and differentiation for fracture repair

Kegelman

Nijsure

Moharrer

et al. 2020

Preprint

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In response to bone fracture, periosteal progenitor cells proliferate, expand, and differentiate to form cartilage and bone in the fracture callus. These cellular functions require the coordinated activation of multiple transcriptional programs, and the transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) regulate osteochondroprogenitor activation during endochondral bone development.However, recent observations raise important distinctions between the signaling mechanisms used to control bone morphogenesis and repair. Here, we tested the hypothesis that YAP and TAZ regulate osteochondroprogenitor activation during endochondral bone fracture healing. Constitutive YAP and/or TAZ deletion from Osterixexpressing cells impaired both cartilage callus formation and subsequent mineralization. However, this could be explained either by direct defects in osteochondroprogenitor differentiation after fracture, or by developmental deficiencies in the progenitor cell pool prior to fracture. Consistent with the second possibility, we found that developmental YAP/TAZ deletion produced long bones with impaired periosteal thickness and cellularity. Therefore, to remove the contributions of developmental history, we next generated adult onset-inducible knockout mice (using Osx1-Cre tetOff ) in which YAP and TAZ were deleted prior to fracture, but after normal development. Adult onset-induced YAP/TAZ deletion had no effect on cartilaginous callus formation, but impaired bone formation at 14 days post-fracture (dpf). Earlier, at 4 dpf, adult onset-induced YAP/TAZ deletion impaired the proliferation and expansion of osteoblast precursor cells located in the shoulder of the callus. Further, activated periosteal cells isolated from this region at 4 dpf exhibited impaired osteogenic differentiation in vitro upon YAP/TAZ deletion. Finally, confirming the effects on osteoblast function in vivo, adult onset-induced YAP/TAZ deletion impaired bone formation in the callus shoulder at 7 dpf, prior to the initiation of endochondral ossification. Together, these data show that YAP and TAZ promote the expansion and differentiation of periosteal osteoblast precursors to accelerate bone fracture healing.

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“…The major advantage of the external fixator is that it is fixed to the bone at some distance from the osteotomy and thus does not directly interfere with the healing process. Furthermore, the external fixator is easily removed post mortem (Haffner-Luntzer et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Radiologic, Ultrasonic and pathological assessments of locally applied Chitosan on promotion of experimentally induced tibial fracture healing in rats

Kotb

Ragab

Fathy

et al. 2020

Journal of Veterinary Medical Research

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ARTICLE INFOThe objective of the present study was to evaluate the ability of Chitosan to promote induced tibial fracture healing in a rat model. The study was conducted on 14 albino rats divided into two equal groups (seven rats in each group). The first group was considered as a control group. The second group was injected Chitosan solution 0.1 mg/kg into the fracture gap. The progress of healing in each group was evaluated by clinical, radiography, ultrasonography and pathological examinations. The healing process was observed to be superior in the Chitosan group compared to the control one. Chitosan was found to promote healing of injured bone and is suggested to be used in cases of complicated or delayed bone fracture.

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Mouse Models in Bone Fracture Healing Research

Cited by 55 publications

References 116 publications

Review of Animal Models of Comorbidities in Fracture‐Healing Research

Review of Animal Models of Comorbidities in Fracture‐Healing Research

YAP and TAZ promote periosteal osteoblast precursor expansion and differentiation for fracture repair

Radiologic, Ultrasonic and pathological assessments of locally applied Chitosan on promotion of experimentally induced tibial fracture healing in rats

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