scholarly journals Fracture Healing via Periosteal Callus Formation Requires Macrophages for Both Initiation and Progression of Early Endochondral Ossification

2014 ◽  
Vol 184 (12) ◽  
pp. 3192-3204 ◽  
Author(s):  
Liza J. Raggatt ◽  
Martin E. Wullschleger ◽  
Kylie A. Alexander ◽  
Andy C.K. Wu ◽  
Susan M. Millard ◽  
...  
2020 ◽  
Vol 6 (45) ◽  
pp. eaaz1410
Author(s):  
Jun Sun ◽  
Heng Feng ◽  
Wenhui Xing ◽  
Yujiao Han ◽  
Jinlong Suo ◽  
...  

Bone fracture is repaired predominantly through endochondral ossification. However, the regulation of endochondral ossification by key factors during fracture healing remains largely enigmatic. Here, we identify histone modification enzyme LSD1 as a critical factor regulating endochondral ossification during bone regeneration. Loss of LSD1 in Prx1 lineage cells severely impaired bone fracture healing. Mechanistically, LSD1 tightly controls retinoic acid signaling through regulation of Aldh1a2 expression level. The increased retinoic acid signaling in LSD1-deficient mice suppressed SOX9 expression and impeded the cartilaginous callus formation during fracture repair. The discovery that LSD1 can regulate endochondral ossification during fracture healing will benefit the understanding of bone regeneration and have implications for regenerative medicine.


Author(s):  
Samuel Crompton ◽  
Fabrizio Messina ◽  
Gillian Klafkowski ◽  
Christine Hall ◽  
Amaka C. Offiah

Abstract Background Recent studies have analysed birth-related clavicular fractures to propose time frames for healing that could be applied to dating of all fractures in cases of suspected child abuse. Objective To assess differences in healing rates between femoral fractures and birth-related clavicular fractures in infants and young children. Materials and methods A retrospective 5-year pilot study of femoral fractures in children younger than 3 years of age was performed. Anonymised radiographs were independently scored by two radiologists for stages of fracture healing. In cases of reader disagreement, radiographs were independently scored by a third radiologist. Results In total, 74 radiographs (30 children) met the inclusion criteria. Fracture healing evolved over time with subperiosteal new bone formation (SPNBF) appearing first, followed by callus then remodelling. A power calculation for a single proportion, with a level of confidence of 95% and a margin of error of 5%, showed that in a definitive study, 359 radiographs would be required. Conclusion Although the overall pattern of healing is similar, in this small pilot study, the earliest times for SPNBF and callus formation in femoral fractures appeared to lag behind healing of birth-related clavicular fractures. Remodelling appeared earlier than remodelling of clavicular fractures. A power calculation has determined numbers of femoral radiographs (359) required for a definitive study.


Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 691
Author(s):  
Jan Barcik ◽  
Devakara R. Epari

The impact of the local mechanical environment in the fracture gap on the bone healing process has been extensively investigated. Whilst it is widely accepted that mechanical stimulation is integral to callus formation and secondary bone healing, treatment strategies that aim to harness that potential are rare. In fact, the current clinical practice with an initially partial or non-weight-bearing approach appears to contradict the findings from animal experiments that early mechanical stimulation is critical. Therefore, we posed the question as to whether optimizing the mechanical environment over the course of healing can deliver a clinically significant reduction in fracture healing time. In reviewing the evidence from pre-clinical studies that investigate the influence of mechanics on bone healing, we formulate a hypothesis for the stimulation protocol which has the potential to shorten healing time. The protocol involves confining stimulation predominantly to the proliferative phase of healing and including adequate rest periods between applications of stimulation.


2020 ◽  
Vol 8 (2) ◽  
pp. e001129
Author(s):  
Takahiro Oda ◽  
Takahiro Niikura ◽  
Tomoaki Fukui ◽  
Keisuke Oe ◽  
Yu Kuroiwa ◽  
...  

IntroductionDiabetes mellitus (DM) negatively affects fracture repair by inhibiting endochondral ossification, chondrogenesis, callus formation, and angiogenesis. We previously reported that transcutaneous CO2 application accelerates fracture repair by promoting endochondral ossification and angiogenesis. The present study aimed to determine whether CO2 treatment would promote fracture repair in cases with type I DM.Research design and methodsA closed femoral shaft fracture was induced in female rats with streptozotocin-induced type I DM. CO2 treatment was performed five times a week for the CO2 group. Sham treatment, where CO2 was replaced with air, was performed for the control group. Radiographic, histologic, genetic, and biomechanical measurements were taken at several time points.ResultsRadiographic assessment demonstrated that fracture repair was induced in the CO2 group. Histologically, accelerated endochondral ossification and capillary formation were observed in the CO2 group. Immunohistochemical assessment indicated that early postfracture proliferation of chondrocytes in callus was enhanced in the CO2 group. Genetic assessment results suggested that cartilage and bone formation, angiogenesis, and vasodilation were upregulated in the CO2 group. Biomechanical assessment revealed enhanced mechanical strength in the CO2 group.ConclusionsOur findings suggest that CO2 treatment accelerates fracture repair in type I DM rats. CO2 treatment could be an effective strategy for delayed fracture repair due to DM.


2012 ◽  
Vol 75 (1) ◽  
pp. 7-14 ◽  
Author(s):  
Lauren Nicole Miller Hayward ◽  
Chantal Marie-Jeanne DE Bakker ◽  
Hrvoje Lusic ◽  
Louis Charles Gerstenfeld ◽  
Mark W. Grinstaff ◽  
...  

2020 ◽  
Author(s):  
Brya G Matthews ◽  
Francesca V Sbrana ◽  
Sanja Novak ◽  
Jessica L. Funnell ◽  
Ye Cao ◽  
...  

AbstractThe periosteum is the major source of cells involved in fracture healing. We sought to characterize differences in progenitor cell populations between periosteum and other bone compartments, and identify periosteal cells involved in fracture healing. The periosteum is highly enriched for progenitor cells, including Sca1+ cells, CFU-F and label-retaining cells. Lineage tracing with αSMACreER identifies periosteal cells that contribute to >80% of osteoblasts and ~40% of chondrocytes following fracture. A subset of αSMA+ cells are quiescent long-term injury-responsive progenitors. Ablation of αSMA+ cells impairs fracture callus formation. In addition, committed osteoblast-lineage cells contributed around 10% of osteoblasts, but no chondrocytes in fracture calluses. Most periosteal progenitors, particularly those that form osteoblasts, can be targeted by αSMACreER. We have demonstrated that the periosteum is highly enriched for skeletal stem and progenitor cells and there is heterogeneity in the populations of cells that contribute to mature lineages during periosteal fracture healing.


2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Peizhen Zhang ◽  
Pengdong Li ◽  
Shihai Liao ◽  
Xuan Li ◽  
Wufan Chen ◽  
...  

The positive effect of low-intensity pulsed ultrasound (LIPUS) on bone fracture healing has been proved. However, during the period of LIPUS therapy, it is undetermined whether LIPUS promotes the formation of heterotopic ossification (HO), which usually occurs in muscle tissues after trauma such as bone fracture and spinal cord injury. Here, we used 6-week LIPUS therapy in a 42-year-old Chinese male patient with a fracture nonunion in combination with ultrasonography for monitoring fracture healing and HO formation. After the LIPUS therapy, the mineralized bone formation in the area of defect of the distal tibia was presented in an ultrasound image, which was consistent with the outcome of plain radiography showing callus formation and the blurred fracture line in the area exposed to LIPUS. In addition, ultrasound images revealed no evidence of HO development within soft tissues during the period of LIPUS therapy. This study suggests that ultrasonography is a potential tool to guarantee the performance of LIPUS therapy with monitoring HO formation. Easy to use, the integration of the handheld ultrasound scanner and the ultrasonic therapeutic apparatus is entirely dedicated to help orthopedists make high-quality care and diagnosis.


2017 ◽  
Vol 20 (02) ◽  
pp. 1750010
Author(s):  
Myung-Sang Moon ◽  
Dong-Hyeon Kim ◽  
Bong-Keun Park ◽  
Min-Geun Yoon

Design: Study on the union pattern of femoral shaft fractures after interlocked intramedullary fixation. Objective: To assess the fracture healing pattern — the so-called callus types — and its formation speed, and age influence. Setting: Orthopedic and traumatic services. Material and methods: Among all the healed femoral shaft fractures, 10 patients at least in each decade from late teens to eighth decade who were regularly followed radiographically with a certain interval upto complete fracture union were chosen. Results: All the fractures healed primarily with external periosteal callus which was followed sometimes later by intercortical uniting callus with disappearance of fracture line. Conclusion: All the nailed femoral shaft fractures healed primarily by periosteal bridging callus irrespective of age, fracture type, and use of interlocking screws, though some less external callus formation after sixth decade was observed.


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