scholarly journals Gukang Capsule Promotes Fracture Healing by Activating BMP/SMAD and Wnt/β-Catenin Signaling Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xue Ma ◽  
Jian Yang ◽  
Ting Liu ◽  
Jing Li ◽  
Yanyu Lan ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Signaling Pathways ◽  
Bone Fractures ◽  
Glycogen Synthase ◽  
Fracture Site ◽  
Bone Morphogenetic Protein 2 ◽  
Radius Fracture ◽  
Smad Signaling ◽  
Alp Activity ◽  
Human Osteosarcoma Cells

Background. Gukang capsule (GKC) is a traditional Chinese medicine formulation which has been used extensively in the clinical treatment of bone fractures. However, the mechanisms underlying its effects on fracture healing remain unclear. Methods. In this study we used a rabbit radius fracture model, and we measured the serum content of bone alkaline phosphatase (ALP), calcium, and phosphorus and examined pathology of the fracture site as indicators of the fracture healing effects of GKC. SaOS-2 human osteosarcoma cells were used to measure (i) ALP activity, (ii) ornithine transcarbamylase (OTC), calcium, and mineralization levels, (iii) the expression of osteogenic-related genes, that is, runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2), collagen I (COL-I), osteopontin (OPN), OTC, and osterix (Osx), and (iv) the expression of key proteins in the Wnt/β-catenin and BMP/SMAD signaling pathways to study the mechanisms by which GKC promotes fracture healing. Results. We found that GKC effectively promotes radius fracture healing in rabbits and enhances ALP activity, increases OTC and calcium levels, and stimulates the formation of mineralized nodules in SaOS-2 cells. Moreover, COL-I, OTC, Osx, BMP2, and OPN expression levels were higher in SaOS-2 cells treated with GKC than control cells. GKC upregulates glycogen synthase kinase 3β (GSK3β) phosphorylation and Smad1/5 and β-catenin protein levels, thereby activating Wnt/β-catenin and BMP/Smad signaling pathways. Inhibitors of the Wnt/β-catenin and BMP/Smad signaling pathways (DKK1 and Noggin, respectively) suppress the osteogenic effects of GKC. Conclusions. GKC promotes fracture healing by activating the Wnt/β-catenin and BMP/Smad signaling pathways and increasing osteoprotegerin (OPG) secretion by osteoblasts (OBs), which prevents receptor activator of nuclear factor kappa B ligand (RANKL) binding to RANK.

scholarly journals Possible Involvement of Smad Signaling Pathways in Induction of Odontoblastic Properties in KN-3 Cells by Bone Morphogenetic Protein-2: A Growth Factor to Induce Dentin Regeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ayako Washio ◽  
Chiaki Kitamura ◽  
Takahiko Morotomi ◽  
Masamichi Terashita ◽  
Tatsuji Nishihara
Keyword(s):  
Signaling Pathways ◽  
Bone Morphogenetic Protein ◽  
Intracellular Signaling ◽  
Matrix Protein ◽  
Molecular Mechanisms ◽  
Bone Morphogenetic Protein 2 ◽  
Smad Signaling ◽  
Dentin Matrix Protein ◽  
Alp Activity ◽  
Morphogenetic Protein

We examined the effects of bone morphogenetic protein-2 (BMP-2) on growth, differentiation, and intracellular signaling pathways of odontoblast-like cells, KN-3 cells, to clarify molecular mechanisms of odontoblast differentiation during pulp regeneration process. After treatment with BMP-2, the cell morphology, growth, alkaline phosphatase (ALP) activity, and the activation and expression of BMP-induced intracellular signaling molecules, such as Smad1/5/8 and Smad6/7, as well as activities of dentin sialoprotein (DSP) and dentin matrix protein 1 (DMP1), were examined. BMP-2 had no effects on the morphology, growth, or ALP activity of KN-3 cells, whereas it induced the phosphorylation of Smad1/5/8 and expression of Smad6/7. BMP-2 also induced the expressions of DSP and DMP-1. Our results suggest that KN-3 cells may express an odontoblastic phenotype with the addition of BMP-2 through the activation of Smad signaling pathways.

scholarly journals Amygdalin Promotes Fracture Healing through TGF-β/Smad Signaling in Mesenchymal Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Jun Ying ◽  
Qinwen Ge ◽  
Songfeng Hu ◽  
Cheng Luo ◽  
Fengyi Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Fracture Healing ◽  
Bone Fracture ◽  
Transforming Growth Factor ◽  
Bone Fractures ◽  
Conditional Knockout ◽  
Mesenchymal Progenitor Cells ◽  
Bone Fracture Healing ◽  
Smad Signaling

Chondrogenesis and subsequent osteogenesis of mesenchymal stem cells (MSCs) and angiogenesis at injured sites are crucial for bone fracture healing. Amygdalin, a cyanogenic glycoside compound derived from bitter apricot kernel, has been reported to inhibit IL-1β-induced chondrocyte degeneration and to stimulate blood circulation, suggesting a promising role of amygdalin in fracture healing. In this study, tibial fractures in C57BL/6 mice were treated with amygdalin. Fracture calluses were then harvested and subjected to radiographic, histological, and biomechanical testing, as well as angiography and gene expression analyses to evaluate fracture healing. The results showed that amygdalin treatment promoted bone fracture healing. Further experiments using MSC-specific transforming growth factor- (TGF-) β receptor 2 conditional knockout (KO) mice (Tgfbr2Gli1-Cre) and C3H10 T1/2 murine mesenchymal progenitor cells showed that this effect was mediated through TGF-β/Smad signaling. We conclude that amygdalin could be used as an alternative treatment for bone fractures.

BOSENTAN, A NON-SPECIFIC ENDOTHELIN ANTAGONIST, STIMULATES FRACTURE HEALING

2007 ◽  
Vol 19 (01) ◽  
pp. 37-46 ◽  
Author(s):  
Hasan H. Muratli ◽  
Feza Korkusuz ◽  
Petek Korkusuz ◽  
Ali Bicimoglu ◽  
Z. Sevim Ercan
Keyword(s):  
Fracture Healing ◽  
Bone Fractures ◽  
Fracture Site ◽  
Controlled Study ◽  
Prostaglandin E ◽  
Matrix Mineralization ◽  
Hind Limbs ◽  
Diaphyseal Bone ◽  
Activity Measurements ◽  
Intramedullary Rod

It is assumed that bosentan, a non-selective ET-1 receptor antagonist, will enhance fracture healing. The aim of this prospective randomized controlled study was to investigate the effects of transcutaneous bosentan administration into diaphyseal bone fractures using radiology, histology, prostaglandin E2 (PGE2) and leukotrien C 4 (LTC4) activity measurements. A closed diaphyseal fracture was created in the hind limbs following intramedullary rod fixation of Guinea pigs. Bosentan was administred by repetitive weekly 0.1 μg transcutaneous injections into the fracture site. The effects of bosentan were evaluated by radiology and histology on weeks 1, 2 and 4, whereas prostaglandin E2 (PGE2)-like and leukotrien C 4 (LTC4)-like activity was assessed on weeks 1 and 2. The radiological degree of union (p = 0.001) at the fracture site and cortex-callus ratio (p = 0.02) was significantly better in the bosentan administered site at week 1 when compared to the control. Histology presented an initial stimulation of bone formation on weeks 1 and 2 in the experimental group. PGE2-like activity was significantly higher (p = 0.002) on week 1 and 2 in the bosentan-administered side. LTC4-like activity remained constant on week one and decreased on week two. Transcutaneous repetitive bosentan administration into the fracture site initially stimulated periosteal bone healing that resulted with extracellular matrix mineralization. The inflammatory mediators PGE2/LTC4 played a significant role in this process.

Contrast-Enhanced Computed Tomography for Non-Destructive, Quantitative Assessment of the Early Stages of Fracture Healing

2011 ◽  
Author(s):  
C. M. J. De Bakker ◽  
L. N. M. Hayward ◽  
L. C. Gerstenfeld ◽  
M. W. Grinstaff ◽  
E. F. Morgan
Keyword(s):  
Computed Tomography ◽  
Fracture Healing ◽  
Bone Fractures ◽  
The United States ◽  
Fracture Site ◽  
Early Assessment ◽  
Subsequent Formation ◽  
Substantial Impact ◽  
Early Stages ◽  
Enhanced Computed Tomography

Each year in the United States, approximately 600,000 bone fractures show delayed or impaired healing and require subsequent surgical intervention1. Techniques for early identification of these cases are presently lacking but could make substantial impact on reducing the morbidity and costs associated with poor bone healing. A current barrier to early assessment of fracture healing is the difficulty in visualizing the cartilaginous “soft” callus that forms at the fracture site in the early stages of repair. The soft callus serves to partially stabilize the fracture and provides a template for subsequent formation of the bony “hard” callus2. Although measurement or estimation of the size, stiffness, and strength of the hard callus is possible by x-ray or computed tomography (CT)3, no analogous methods have been developed for the soft callus, due to the low radio-opacity of cartilage.

scholarly journals Effect of bovine bone morphogenetic proteins on radius fracture healing in rabbits

2007 ◽  
Vol 22 (4) ◽  
pp. 260-265 ◽  
Author(s):  
Alfredo Feio da Maia Lima ◽  
Sheila Canevese Rahal ◽  
Reinaldo dos Santos Volpi ◽  
José Mauro Granjeiro ◽  
Rumio Taga ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Morphogenetic Proteins ◽  
Histological Analysis ◽  
Experimental Period ◽  
Fracture Site ◽  
Radius Fracture ◽  
Bovine Bone ◽  
Bone Area ◽  
Bovine Collagen ◽  
Fracture Consolidation

PURPOSE: To investigate the effect of bovine bone morphogenetic proteins (bBMPs) bound to hydroxyapatite plus collagen in the healing of unstable radius fractures. METHODS: A transverse fracture was induced at the mid of the diaphysis in both radii on 15 Norfolk rabbits with average age of 5.5 months and 3.5kg. A mixture of bBMPs bound to thin powdered hydroxyapatite (bBMP-HA) and bovine collagen as agglutinant was applied to the right radius fracture site. The left radius fracture was considered control and no treatment was used. After 30, 60 and 90 days (5 rabbits/period) the rabbits were euthanized and the radii were collected for histological analysis. RESULTS: The descriptive histological analysis revealed that repair was similar for both forelimbs. The histomorphometric analysis showed that the mean area of newly formed bone was 867442.16 mm², 938743.00 mm² and 779621.06 mm² for the control forelimbs, and 841118.47 mm², 788038.76mm² and 618587.24 mm² for the treated forelimbs at 30, 60 and 90 days, respectively. Thus the newly formed bone area was 12.17% larger in the forelimbs treated with bBMP-HA/collagen than in the control forelimbs (p<0.05, Tukey test) in the 60-day period after surgery. In both forelimbs the newly formed bone area increased throughout the experimental period until the complete fracture healing. CONCLUSION: Based on the result obtained here we concluded that bBMP-HA/collagen induced a lower but significant improvement in fracture consolidation.

scholarly journals Lithium for Fracture Treatment (LiFT): a double-blind randomised control trial protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. e031545 ◽  
Author(s):  
Diane Nam ◽  
Phumeena Balasuberamaniam ◽  
Katrine Milner ◽  
Monica Kunz ◽  
Kathak Vachhani ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Fractures ◽  
Fracture Site ◽  
Long Bone ◽  
Randomised Control Trial ◽  
Secondary Outcome ◽  
Double Blind ◽  
Carbonate Group ◽  
Main Trial ◽  
Radiographic Union

IntroductionFracture healing can fail in up to 10% of cases despite appropriate treatment. While lithium has been the standard treatment for bipolar disorder, it may also have a significant impact to increase bone healing in patients with long bone fractures. To translate this knowledge into clinical practice, a randomised clinical trial (RCT) is proposed.Methods and analysisA multicentre double blind, placebo-controlled RCT is proposed to evaluate the efficacy of lithium to increase the rate and predictability of long bone fracture healing in healthy adults compared to lactose placebo treatment. 160 healthy individuals from 18 to 55 years of age presenting with shaft fractures of the femur, tibia/fibula, humerus or clavicle will be eligible. Fractures will be randomised to placebo (lactose) or treatment (300 mg lithium carbonate) group within 2 weeks of the injury. The primary outcome measure will be radiographic union defined as visible callus bridging on three of the four cortices at the fracture site using a validated radiographic union score. Secondary outcome measures will include functional assessment and pain scoring.Ethics and disseminationParticipant confidentiality will be maintained with publication of results. Research Ethics Board Approval: Sunnybrook Research Institute (REB # 356–2016). Health Canada Approval (HC6-24-C201560). Results of the main trial and secondary endpoints will be submitted for publication in a peer-reviewed journal and presented at conferences.Trial registration numberNCT02999022.

Effect of Intramedullary Nailing Patterns On Interfragmentary Strain in a Mouse Femur Fracture: a Parametric Finite Element Analysis

2021 ◽  
Author(s):  
Gregory Lowen ◽  
Katherine Garrett ◽  
Moore-Lotridge Stephanie ◽  
Sasidhar Uppuganti ◽  
Scott A. Guelcher ◽  
...  
Keyword(s):  
Finite Element Analysis ◽  
Finite Element ◽  
Fracture Healing ◽  
Bone Repair ◽  
Bone Fractures ◽  
Fracture Site ◽  
Fracture Repair ◽  
Long Bone ◽  
Design Parameters ◽  
Element Analysis

Abstract Delayed long bone fracture healing and nonunion continue to be a significant socioeconomic burden. While mechanical stimulation is known to be an important determinant of the bone repair process, understanding how the magnitude, mode, and commencement of interfragmentary strain (IFS) affect fracture healing can guide new therapeutic strategies to prevent delayed healing or non-union. Mouse models provide a means to investigate the molecular and cellular aspects of fracture repair, yet there is only one commercially available, clinically-relevant, locking intramedullary nail (IMN) currently available for studying long bone fractures in rodents. Having access to alternative IMNs would allow a variety of mechanical environments at the fracture site to be evaluated, and the purpose of this proof-of-concept finite element analysis study is to identify which IMN design parameters have the largest impact on IFS in a murine transverse femoral osteotomy model. Using the dimensions of the clinically relevant IMN as a guide, the nail material, distance between interlocking screws, and clearance between the nail and endosteal surface were varied between simulations. Of these parameters, changing the nail material from stainless steel (SS) to polyetheretherketone (PEEK) had the largest impact on IFS. Reducing the distance between the proximal and distal interlocking screws substantially affected IFS only when nail modulus was low. Therefore, IMNs with low modulus (e.g., PEEK) can be used alongside commercially available SS nails to investigate the effect of initial IFS or stability on fracture healing with respect to different biological conditions of repair in rodents.

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