scholarly journals Akkermansia muciniphila promotes type H vessel formation and bone fracture healing by reducing gut permeability and inflammation

2020 ◽  
Vol 13 (11) ◽  
pp. dmm043620 ◽  
Author(s):  
Jiang-Hua Liu ◽  
Tao Yue ◽  
Zhong-Wei Luo ◽  
Jia Cao ◽  
Zi-Qi Yan ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Systemic Inflammation ◽  
Bone Healing ◽  
Bone Fracture ◽  
Early Stage ◽  
Gut Permeability ◽  
Bone Fracture Healing ◽  
Gut Barrier ◽  
Vessel Formation ◽  
Akkermansia Muciniphila

ABSTRACTImproving revascularization is one of the major measures in fracture treatment. Moderate local inflammation triggers angiogenesis, whereas systemic inflammation hampers angiogenesis. Previous studies showed that Akkermansia muciniphila, a gut probiotic, ameliorates systemic inflammation by tightening the intestinal barrier. In this study, fractured mice intragastrically administrated with A. muciniphila were found to display better fracture healing than mice treated with vehicle. Notably, more preosteclasts positive for platelet-derived growth factor-BB (PDGF-BB) were induced by A. muciniphila at 2 weeks post fracture, coinciding with increased formation of type H vessels, a specific vessel subtype that couples angiogenesis and osteogenesis, and can be stimulated by PDGF-BB. Moreover, A. muciniphila treatment significantly reduced gut permeability and inflammation at the early stage. Dextran sulfate sodium (DSS) was used to disrupt the gut barrier to determine its role in fracture healing and whether A. muciniphila still can stimulate bone fracture healing. As expected, A. muciniphila evidently improved gut barrier, reduced inflammation and restored the impaired bone healing and angiogenesis in DSS-treated mice. Our results suggest that A. muciniphila reduces intestinal permeability and alleviates inflammation, which probably induces more PDGF-BB+ preosteoclasts and type H vessel formation in callus, thereby promoting fracture healing. This study provides the evidence for the involvement of type H vessels in fracture healing and suggests the potential of A. muciniphila as a promising strategy for bone healing.This article has an associated First Person interview with the first author of the paper.

scholarly journals Role of Dynamic Loading on Early Stage of Bone Fracture Healing

2018 ◽  
Vol 46 (11) ◽  
pp. 1768-1784 ◽  
Author(s):  
Smriti Ghimire ◽  
Saeed Miramini ◽  
Martin Richardson ◽  
Priyan Mendis ◽  
Lihai Zhang
Keyword(s):  
Fracture Healing ◽  
Dynamic Loading ◽  
Bone Fracture ◽  
Early Stage ◽  
Bone Fracture Healing

PREDICTION OF THE TREND OF BONE FRACTURE HEALING BASED ON THE RESULTS OF THE EARLY STAGES SIMULATIONS: A FINITE ELEMENT STUDY

2019 ◽  
Vol 19 (05) ◽  
pp. 1950021
Author(s):  
JALIL NOURISA ◽  
GHOLAMREZA ROUHI
Keyword(s):  
Finite Element ◽  
Fracture Healing ◽  
Bone Fracture ◽  
Mechanical Stability ◽  
Early Stage ◽  
Healing Process ◽  
Fibrous Tissue ◽  
Fe Model ◽  
Bone Fracture Healing ◽  
Early Stages

To date, several studies have implied the importance of early stage mechanical stability in the bone fracture healing process. This study aimed at finding a correlation between the predicted different tissue phenotypes in the early stages of healing and the ultimate healing outcome. For this purpose, the process of fracture healing was numerically simulated employing an axisymmetric bi-phasic finite element (FE) model for three initial gap sizes of 1, 3 and 6[Formula: see text]mm and four initial interfragmentary strains (IFS) of 7%, 11%, 15% and 19%. The model was validated with experimental and other numerical studies from the literature. Results of this study showed that the amount of cartilage and fibrous tissue observed in the early stage after fracture can be used to qualitatively assess the outcome of complete bone healing process. Greater amount of cartilage in early stage of healing process yielded faster callus maturation, and delayed maturation of callus was predicted in the case of high fibrous tissue production. Results of this study can be used to provide an estimation of the performance of different fixation systems by considering the amounts of cartilage and fibrous tissues observed in the early stage of healing.

scholarly journals Analysis of low-dose estrogen on callus BMD as measured by pQCT in postmenopausal women

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
K. Jäckle ◽  
J. P. Kolb ◽  
A. F. Schilling ◽  
C. Schlickewei ◽  
M. Amling ◽  
...  
Keyword(s):  
Bone Density ◽  
Beneficial Effect ◽  
Fracture Healing ◽  
Postmenopausal Women ◽  
Bone Healing ◽  
Bone Fracture ◽  
Low Dose ◽  
Callus Formation ◽  
Trial Registration ◽  
Bone Fracture Healing

Abstract Background Osteoporosis affects elderly patients of both sexes. It is characterized by an increased fracture risk due to defective remodeling of the bone microarchitecture. It affects in particular postmenopausal women due to their decreased levels of estrogen. Preclinical studies with animals demonstrated that loss of estrogen had a negative effect on bone healing and that increasing the estrogen level led to a better bone healing. We asked whether increasing the estrogen level in menopausal patients has a beneficial effect on bone mineral density (BMD) during callus formation after a bone fracture. Methods To investigate whether estrogen has a beneficial effect on callus BMD of postmenopausal patients, we performed a prospective double-blinded randomized study with 76 patients suffering from distal radius fractures. A total of 31 patients (71.13 years ±11.99) were treated with estrogen and 45 patients (75.62 years ±10.47) served as untreated controls. Calculated bone density as well as cortical bone density were determined by peripheral quantitative computed tomography (pQCT) prior to and 6 weeks after the surgery. Comparative measurements were performed at the fractured site and at the corresponding position of the non-fractured arm. Results We found that unlike with preclinical models, bone fracture healing of human patients was not improved in response to estrogen treatment. Furthermore, we observed no dependence between age-dependent bone tissue loss and constant callus formation in the patients. Conclusions Transdermally applied estrogen to postmenopausal women, which results in estrogen levels similar to the systemic level of premenopausal women, has no significant beneficial effect on callus BMD as measured by pQCT, as recently shown in preclinical animal models. Trial registration Low dose estrogen has no significant effect on bone fracture healing measured by pQCT in postmenopausal women, DRKS00019858. Registered 25th November 2019 - Retrospectively registered. Trial registration number DRKS00019858.

scholarly journals Management of impaired fracture healing: Historical aspects

2005 ◽  
Vol 58 (9-10) ◽  
pp. 507-512
Author(s):  
Djordje Gajdobranski ◽  
Ivan Micic ◽  
Milorad Mitkovic ◽  
Desimir Mladenovic ◽  
Miroslav Milankov
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Bone Fracture ◽  
Human Life ◽  
Historical Review ◽  
Treatment Modalities ◽  
Bone Fracture Healing ◽  
Ancient Medicine ◽  
Adequate Treatment ◽  
Orthopedic Surgeons

Introduction Establishing continuity of long bones in cases of impaired bone healing and pseudo-arthrosis is one of the most complex problems in orthopedics. Impaired bone healing The problem of impaired fracture healing is not new. As in other areas of human life, the roots of modern treatment of impaired bone healing lie in ancient medicine. A relatively high percentage of impaired bone healing, as well as unsatisfactory results of standard therapies of impaired bone healing and pseudoarthrosis demonstrate the actuality of this problem. This paper represents an attempt to pay respect to some of those who have dedicated their work to this problem in orthopedic surgery, and it is a historical review on impaired bone fracture healing. At the same time it should be an additional stimulus and challenge for orthopedic surgeons to further study impaired bone fracture healing, improve the existing and find new methods for their adequate treatment. Conclusion The authors are certain that the number of researchers throughout the world who have contributed to treatment modalities of impaired bone healing, is much higher, but not all are mentioned in this paper. However, it does not lessen their contributions to orthopedics.

scholarly journals Influence of high-frequency cyclical stimulation on the bone fracture-healing process: mathematical and experimental models

2011 ◽  
Vol 369 (1954) ◽  
pp. 4278-4294 ◽  
Author(s):  
María José Gómez-Benito ◽  
Libardo Andrés González-Torres ◽  
Esther Reina-Romo ◽  
Jorge Grasa ◽  
Belén Seral ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Mechanical Stimulation ◽  
Bone Fracture ◽  
High Frequency ◽  
Endochondral Ossification ◽  
Healing Process ◽  
Bone Fracture Healing ◽  
Bone Healing Process ◽  
Low Magnitude

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.

scholarly journals Analysis of low-dose estrogen on callus BMD as measured by pQCT in postmenopausal women

2020 ◽  
Author(s):  
Katharina Blanka Dr. Jäckle ◽  
Jan Philipp Kolb ◽  
Arndt F Schilling ◽  
Carsten Schlickewei ◽  
Michael Amling ◽  
...  
Keyword(s):  
Bone Density ◽  
Beneficial Effect ◽  
Fracture Healing ◽  
Postmenopausal Women ◽  
Bone Healing ◽  
Bone Fracture ◽  
Low Dose ◽  
Callus Formation ◽  
Trial Registration ◽  
Bone Fracture Healing

Abstract Background: Osteoporosis affects elderly patients of both sexes. It is characterized by an increased fracture risk due to defective remodeling of the bone microarchitecture. It affects in particular postmenopausal women due to their decreased levels of estrogen. Preclinical studies with animals demonstrated that loss of estrogen had a negative effect on bone healing and that increasing the estrogen level led to a better bone healing. We asked whether increasing the estrogen level in menopausal patients has a beneficial effect on bone mineral density (BMD) during callus formation after a bone fracture.Methods: To investigate whether estrogen has a beneficial effect on callus BMD of postmenopausal patients, we performed a prospective double-blinded randomized study with 76 patients suffering from distal radius fractures. A total of 31 patients (71.13 years ± 11.99) were treated with estrogen and 45 patients (75.62 years ± 10.47) served as untreated controls. Calculated bone density as well as cortical bone density were determined by peripheral quantitative computed tomography (pQCT) prior to and six weeks after the surgery. Comparative measurements were performed at the fractured site and at the corresponding position of the non-fractured arm.Results: We found that unlike with preclinical models, bone fracture healing of human patients was not improved in response to estrogen treatment. Furthermore, we observed no dependence between age-dependent bone tissue loss and constant callus formation in the patients.Conclusions: Transdermally applied estrogen to postmenopausal women, which results in estrogen levels similar to the systemic level of premenopausal women, has no significant beneficial effect on callus BMD as measured by pQCT, as recently shown in preclinical animal models.Trial registration: Low dose estrogen has no significant effect on bone fracture healing measured by pQCT in postmenopausal women, DRKS00019858. Registered 25th November 2019 - Retrospectively registered. Trial registration number DRKS00019858.

scholarly journals First person – Jiang-Hua Liu

2020 ◽  
Vol 13 (11) ◽  
pp. dmm047670
Keyword(s):  
Bone Fracture ◽  
Early Career ◽  
Disease Models ◽  
First Person ◽  
Gut Permeability ◽  
Bone Fracture Healing ◽  
Vessel Formation ◽  
Early Career Researchers ◽  
Central South ◽  
Selection Of

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Jiang-Hua Liu is first author on ‘Akkermansia muciniphila promotes type H vessel formation and bone fracture healing by reducing gut permeability and inflammation’, published in DMM. Jiang-Hua is a PhD student in the lab of Hui Xie in the Department of Orthopaedics, Xiangya Hospital, Central South University, China, investigating how A. muciniphila promotes type H vessel formation in callus of fractured bone.

The Effects of Flexible Fixation on Early Stage Bone Fracture Healing

2013 ◽  
Vol 3 (2) ◽  
pp. 181 ◽  
Author(s):  
Lihai Zhang ◽  
Saeed Miramini ◽  
Priyan Mendis ◽  
Martin Richardson ◽  
Marinis Pirpiris ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Fracture ◽  
Early Stage ◽  
Bone Fracture Healing

scholarly journals The Effects of TMP Treatment and High Fat Diet on Bone Fracture Healing

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Samuel Zike ◽  
Jeffery Nielsen ◽  
Caio De Andrade Staut ◽  
Vincent Alentado ◽  
Ushashi Dadwal ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Bone Fracture ◽  
High Fat Diet ◽  
Saline Control ◽  
Diabetic Patients ◽  
High Fat ◽  
Bone Fracture Healing ◽  
Orthopaedic Surgeons

Delayed and impaired bone fracture healing are associated with diabetic populations. This is a challenging problem for orthopaedic surgeons especially in the US where the percentage of type 2 diabetic patients continues to climb at an alarming rate. Limited treatment options exist for orthopaedic surgeons to improve fracture healing, and the most commonly used therapies involve placement of proteins (bone morphogenetic protein), graft tissue, or demineralized bone matrix at the fracture site. We have previously demonstrated that local administration of the main megakaryocyte growth factor, thrombopoietin, enhances bone healing. Here we demonstrate the utility of systemically administering thrombopoietin mimetic peptides (TMPs) to improve impaired fracture healing in a mouse model of type 2 diabetes. Briefly, 120 male mice on a C57BL/6 background were placed on a low fat diet (LFD) or high fat diet (HFD) for 12 weeks prior to undergoing a surgically created femoral fracture. Mice were treated with 33 nmol/kg of TMP or saline immediately after surgery and daily for the following week. Mice were euthanized at 1, 2, and 4 weeks post-surgery (n=10/group). Here, we confirmed that HFD resulted in impaired fracture healing. We also showed accelerated bone union and increased callus formation in TMP treated mice compared to saline groups, irrespective of diet (p<0.05). Among TMP groups that were fed either a HFD or LFD, the HFD TMP group showed greater improvements in bone healing compared to the HFD saline control mice. Further study on TMP should include alternative routes of administration and providing treatment when a surgical repair appears to be deteriorating. Although there is more to be understood about the clinical importance and mechanism by which systemic TMP treatment enhances fracture healing, these data appear promising.

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