External Beam Irradiation Preferentially Inhibits the Endochondral Pathway of Fracture Healing: A Rat Model

Wu, Yongren; Hanna, Eissa; Holmes, R.; Lin, Zilan; Chiaramonti, Alexander; Reeves, Russell A.; McDonald, D. G.; Vanek, K; Barfield, William R.; Yao, Haimin; Pellegrini, Vincent D.

doi:10.1097/corr.0000000000000395

Cited by 6 publications

(3 citation statements)

References 53 publications

(73 reference statements)

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“…Similarly, pre- and post-operative radiation treatments have been associated with changes in fracture healing. Whereas high dose x-ray radiation (5–8 Gy) was associated with an impairment of fracture healing, lower doses (0.5–1 Gy) accelerated endochondral and intramembranous ossification during the repair process 28–31 . These findings indicate the importance of study-specific adaptation of micro-CT protocols, and to protect animals scanning times and radiation settings should be minimized.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of longitudinal time-lapsed in vivo micro-CT for monitoring fracture healing in mouse femur defect models

Wehrle

Betts

Kuhn

et al. 2019

Sci Rep

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Longitudinal in vivo micro-computed tomography (micro-CT) is of interest to non-invasively capture the healing process of individual animals in preclinical fracture healing studies. However, it is not known whether longitudinal imaging itself has an impact on callus formation and remodeling. In this study, a scan group received weekly micro-CT measurements (week 0–6), whereas controls were only scanned post-operatively and at week 5 and 6. Registration of consecutive scans using a branching scheme (bridged vs. unbridged defect) combined with a two-threshold approach enabled assessment of localized bone turnover and mineralization kinetics relevant for monitoring callus remodeling. Weekly micro-CT application did not significantly change any of the assessed callus parameters in the defect and periosteal volumes. This was supported by histomorphometry showing only small amounts of cartilage residuals in both groups, indicating progression towards the end of the healing period. Also, immunohistochemical staining of Sclerostin, previously associated with mediating adverse radiation effects on bone, did not reveal differences between groups. The established longitudinal in vivo micro-CT-based approach allows monitoring of healing phases in mouse femur defect models without significant effects of anesthesia, handling and radiation on callus properties. Therefore, this study supports application of longitudinal in vivo micro-CT for healing-phase-specific monitoring of fracture repair in mice.

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Section: Introductionmentioning

confidence: 99%

Evaluation of longitudinal time-lapsed in vivo micro-CT for monitoring fracture healing in mouse femur defect models

Wehrle

Betts

Kuhn

et al. 2019

Sci Rep

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“…The findings of a smaller fracture callus with increased apoptosis were strongly reminiscent of the findings seen in hind-limb irradiation as a model of diminished fracture healing [ 21 , 23 ] We hypothesized the fracture healing phenotype in the KO mice was mediated by an effect of Del1 on BCSPs. The lineage hierarchy of the BCSPs showed that BCSPs were differentiated from Skeletal Stem Cells (SSCs) and could also differentiate into PCP (pro-chondrocyte progenitors), bone and stromal cells.…”

Section: Resultsmentioning

confidence: 97%

Del1 Is a Growth Factor for Skeletal Progenitor Cells in the Fracture Callus

Sun,

Boyko,

Marecic

et al. 2023

Biomolecules

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Failure to properly form bone or integrate surgical implants can lead to morbidity and additional surgical interventions in a significant proportion of orthopedic surgeries. While the role of skeletal stem cells (SSCs) in bone formation and repair is well-established, very little is known about the factors that regulate the downstream Bone, Cartilage, Stromal, Progenitors (BCSPs). BCSPs, as transit amplifying progenitor cells, undergo multiple mitotic divisions to expand the pool of lineage committed progenitors allowing stem cells to preserve their self-renewal and stemness. Del1 is a protein widely expressed in the skeletal system, but its deletion led to minimal phenotype changes in the uninjured mouse. In this paper, we demonstrate that Del1 is a key regulator of BCSP expansion following injury. In Del1 knockout mice, there is a significant reduction in the number of BCSPs which leads to a smaller callus and decreased bone formation compared with wildtype (WT) littermates. Del1 serves to promote BCSP proliferation and prevent apoptosis in vivo and in vitro. Moreover, exogenous Del1 promotes proliferation of aged human BCSPs. Our results highlight the potential of Del1 as a therapeutic target for improving bone formation and implant success. Del1 injections may improve the success of orthopedic surgeries and fracture healing by enhancing the proliferation and survival of BCSPs, which are crucial for generating new bone tissue during the process of bone formation and repair.

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“…Similarly, pre- and post-operative radiation treatments have been associated with changes in fracture healing. Whereas high dose x-ray radiation (5-8Gy) was associated with an impairment of fracture healing, lower doses (0.5-1Gy) accelerated endochondral and intramembranous ossification during the repair process 28–31 . These findings indicate the importance of study-specific adaptation of micro-CT protocols, and to protect animals scanning times and radiation settings should be minimized.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of longitudinal time-lapsedin vivomicro-CT for monitoring fracture healing in mouse femur defect models

Wehrle

Betts

Kuhn

et al. 2019

Preprint

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External Beam Irradiation Preferentially Inhibits the Endochondral Pathway of Fracture Healing: A Rat Model

Abstract: This work suggests that there may be a rationale for compression plating rather than intramedullary nailing of long bone fractures in select circumstances where bony union is desirable, adjunctive radiation treatment is required, and bone stock is sufficient for plate and screw fixation.

Cited by 6 publications

References 53 publications

Evaluation of longitudinal time-lapsed in vivo micro-CT for monitoring fracture healing in mouse femur defect models

Evaluation of longitudinal time-lapsed in vivo micro-CT for monitoring fracture healing in mouse femur defect models

Del1 Is a Growth Factor for Skeletal Progenitor Cells in the Fracture Callus

Evaluation of longitudinal time-lapsedin vivomicro-CT for monitoring fracture healing in mouse femur defect models

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