scholarly journals Sonic Hedgehog Regulates Bone Fracture Healing

2020 ◽  
Vol 21 (2) ◽  
pp. 677 ◽  
Author(s):  
Hiroaki Takebe ◽  
Nazmus Shalehin ◽  
Akihiro Hosoya ◽  
Tsuyoshi Shimo ◽  
Kazuharu Irie

Bone fracture healing involves the combination of intramembranous and endochondral ossification. It is known that Indian hedgehog (Ihh) promotes chondrogenesis during fracture healing. Meanwhile, Sonic hedgehog (Shh), which is involved in ontogeny, has been reported to be involved in fracture healing, but the details had not been clarified. In this study, we demonstrated that Shh participated in fracture healing. Six-week-old Sprague–Dawley rats and Gli-CreERT2; tdTomato mice were used in this study. The right rib bones of experimental animals were fractured. The localization of Shh and Gli1 during fracture healing was examined. The localization of Gli1 progeny cells and osterix (Osx)-positive cells was similar during fracture healing. Runt-related transcription factor 2 (Runx2) and Osx, both of which are osteoblast markers, were observed on the surface of the new bone matrix and chondrocytes on day seven after fracture. Shh and Gli1 were co-localized with Runx2 and Osx. These findings suggest that Shh is involved in intramembranous and endochondral ossification during fracture healing.

Author(s):  
María José Gómez-Benito ◽  
Libardo Andrés González-Torres ◽  
Esther Reina-Romo ◽  
Jorge Grasa ◽  
Belén Seral ◽  
...  

Mechanical stimulation affects the evolution of healthy and fractured bone. However, the effect of applying cyclical mechanical stimuli on bone healing has not yet been fully clarified. The aim of the present study was to determine the influence of a high-frequency and low-magnitude cyclical displacement of the fractured fragments on the bone-healing process. This subject is studied experimentally and computationally for a sheep long bone. On the one hand, the mathematical computational study indicates that mechanical stimulation at high frequencies can stimulate and accelerate the process of chondrogenesis and endochondral ossification and consequently the bony union of the fracture. This is probably achieved by the interstitial fluid flow, which can move nutrients and waste from one place to another in the callus. This movement of fluid modifies the mechanical stimulus on the cells attached to the extracellular matrix. On the other hand, the experimental study was carried out using two sheep groups. In the first group, static fixators were implanted, while, in the second one, identical devices were used, but with an additional vibrator. This vibrator allowed a cyclic displacement with low magnitude and high frequency (LMHF) to be applied to the fractured zone every day; the frequency of stimulation was chosen from mechano-biological model predictions. Analysing the results obtained for the control and stimulated groups, we observed improvements in the bone-healing process in the stimulated group. Therefore, in this study, we show the potential of computer mechano-biological models to guide and define better mechanical conditions for experiments in order to improve bone fracture healing. In fact, both experimental and computational studies indicated improvements in the healing process in the LMHF mechanically stimulated fractures. In both studies, these improvements could be associated with the promotion of endochondral ossification and an increase in the rate of cell proliferation and tissue synthesis.


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.


Bone ◽  
2018 ◽  
Vol 106 ◽  
pp. 78-89 ◽  
Author(s):  
Claudia Schlundt ◽  
Thaqif El Khassawna ◽  
Alessandro Serra ◽  
Anke Dienelt ◽  
Sebastian Wendler ◽  
...  

Bone Reports ◽  
2021 ◽  
Vol 14 ◽  
pp. 100740
Author(s):  
Smriti Ghimire ◽  
Saeed Miramini ◽  
Glenn Edwards ◽  
Randi Rotne ◽  
Jiake Xu ◽  
...  

Author(s):  
BRENT R IOYAH ◽  
WIDURINI DJOHAN ◽  
ERIK IDRUS

Objective: Healing of bone fractures is mediated through antioxidants; however, increased free radical levels at the site of fracture inhibit bone healing.Mangosteen peel has antioxidant, anti-inflammatory, antitumor, antiviral, antibacterial, antifungal, antihistaminic, antimalarial, and other beneficialproperties as it contains many active substances such as xanthones, anthocyanins, phenols, and tannins. In this study, we aimed to determine theeffects of mangosteen peel extract on bone fracture healing.Methods: We used six mice with left and right femoral fractures (12 femurs). Mangosteen peel extract was applied to the left femurs of the six mice attwo dosages (20 and 40 mg/kg; three femurs each) on days 2, 4, and 6 after fracture; saline was injected into the right femurs of all six mice. On day 7,all the animals were sacrificed, and femur defect diameter was evaluated using dental digital radiography.Results: The femoral defect diameter in mice treated with 40 mg/kg dose of mangosteen peel extract was less than that in mice treated with saline,although the difference was not significant.Conclusion: Application of a 40 mg/kg dose of mangosteen peel extract promotes bone fracture healing.


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