Effects of blockade of endogenous Gisignaling in Tie2-expressing cells on bone formation in a mouse model of heterotopic ossification

2015 ◽  
Vol 33 (8) ◽  
pp. 1212-1217 ◽  
Author(s):  
Liping Wang ◽  
Dylan O' Carroll ◽  
Xuhui Liu ◽  
Theresa Roth ◽  
Hubert Kim ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Formation ◽  
Heterotopic Ossification

scholarly journals Hedgehog pathway inhibitors significantly reduce the formation of heterotopic ossification in a direct trauma/burn mouse model

2021 ◽  
Author(s):  
Atanu Chakraborty ◽  
Jelena Gvozdenovic-Jeremic ◽  
Fang Wang ◽  
Stephen W. Hoag ◽  
Ekaterina Vert-Wong ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Formation ◽  
Heterotopic Ossification ◽  
Total Joint Replacement ◽  
Combat Trauma ◽  
Therapeutic Benefits ◽  
Elbow Fractures ◽  
Proinflammatory Responses ◽  
Combination Approach ◽  
Musculoskeletal Trauma

AbstractHeterotopic ossification (HO), either acquired or hereditary, is featured by ectopic bone formation outside of the normal skeleton. The acquired form of HO is a debilitating and common complication of musculoskeletal trauma, central nervous system injury, burns, combat trauma, hip and elbow fractures, and total joint replacement surgeries. It can be characterized as abnormal bone formation that occurs mostly by endochondral ossification. Recent studies have implicated inflammation and dysregulation of Hedgehog (Hh) signaling as major early contributors to HO formation. Here, we demonstrate that administration of the Hh pathway inhibitor, arsenic trioxide (ATO), prevented acquired HO in a clinically-relevant trauma/burn mouse model. We further evaluated the effects of two additional Hh pathway antagonists: cholecalciferol and pravastatin on mitigating osteoblast differentiation. Finally, we assessed the effect of a combination of Hh pathway inhibitors on reducing systemic proinflammatory responses. A targeted combination approach using Hh pathway inhibitors may offer potential therapeutic benefits though targeting differential components of the Hh pathway. Taken together, our study demonstrates that the administration of single or multiple Hh pathway inhibitors may have the potential to reduce the formation of acquired HO.

scholarly journals High-frequency spectral ultrasound imaging (SUSI) visualizes early post-traumatic heterotopic ossification (HO) in a mouse model

Bone ◽  
2018 ◽  
Vol 109 ◽  
pp. 49-55 ◽  
Author(s):  
Kavitha Ranganathan ◽  
Xiaowei Hong ◽  
David Cholok ◽  
Joe Habbouche ◽  
Caitlin Priest ◽  
...  
Keyword(s):  
Mouse Model ◽  
Heterotopic Ossification ◽  
Ultrasound Imaging ◽  
High Frequency ◽  
Post Traumatic

scholarly journals Synostosis Between Pubic Bones due to Neurogenic, Heterotopic Ossification

2006 ◽  
Vol 6 ◽  
pp. 2486-2490 ◽  
Author(s):  
Subramanian Vaidyanathan ◽  
Peter L. Hughes ◽  
Bakul M. Soni
Keyword(s):  
Bone Formation ◽  
Heterotopic Ossification ◽  
Foley Catheter ◽  
Symphysis Pubis ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Suprapubic Catheter ◽  
Suprapubic Cystostomy ◽  
Urine Leak ◽  
Irregular Margin

Neurogenic, heterotopic ossification is characterised by the formation of new, extraosseous (ectopic) bone in soft tissue in patients with neurological disorders. A 33-year-old female, who was born with spina bifida, paraplegia, and diastasis of symphysis pubis, had indwelling urethral catheter drainage and was using oxybutynin bladder instillations. She was prescribed diuretic for swelling of feet, which aggravated bypassing of catheter. Hence, suprapubic cystostomy was performed. Despite anticholinergic therapy, there was chronic urine leak around the suprapubic catheter and per urethra. Therefore, the urethra was mobilised and closed. After closure of the urethra, there was no urine leak from the urethra, but urine leak persisted around the suprapubic catheter. Cystogram confirmed the presence of a Foley balloon inside the bladder; there was no urinary fistula. The Foley balloon ruptured frequently, leading to extrusion of the Foley catheter. X-ray of abdomen showed heterotopic bone formation bridging the gap across diastasis of symphysis pubis. CT of pelvis revealed heterotopic bone lying in close proximity to the balloon of the Foley catheter; the sharp edge of heterotopic bone probably acted like a saw and led to frequent rupture of the balloon of the Foley catheter. Unique features of this case are: (1) temporal relationship of heterotopic bone formation to suprapubic cystostomy and chronic urine leak; (2) occurrence of heterotopic ossification in pubic region; (3) complications of heterotopic bone formation viz. frequent rupture of the balloon of the Foley catheter by the irregular margin of heterotopic bone and difficulty in insertion of suprapubic catheter because the heterotopic bone encroached on the suprapubic track; (4) synostosis between pubic bones as a result of heterotopic ossification..Common aetiological factors for neurogenic, heterotopic ossification, such as forceful manipulation, trauma, or spasticity, were absent in this patient. Since heterotopic bone formation was observed in the pubic region after suprapubic cystostomy and chronic urine leak, it is possible that risk factors related to the urinary tract might have played a role in heterotopic bone formation, which resulted in synostosis between pubic bones.

scholarly journals Decreased Bone Formation Explains Osteoporosis in a Genetic Mouse Model of Hemochromatosiss

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0148292 ◽  
Author(s):  
Mathilde Doyard ◽  
Daniel Chappard ◽  
Patricia Leroyer ◽  
Marie-Paule Roth ◽  
Olivier Loréal ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Formation ◽  
Genetic Mouse Model

Pro-osteogenic Effects of WNT in a Mouse Model of Bone Formation Around Femoral Implants

2020 ◽  
Author(s):  
Zhijun Li ◽  
Xue Yuan ◽  
Masaki Arioka ◽  
Daniel Bahat ◽  
Qiang Sun ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Formation ◽  
Femoral Implants

scholarly journals Effects of Systemic and Local Administration of Recombinant Human IGF-I (rhIGF-I) on De Novo Bone Formation in an Aged Mouse Model

2006 ◽  
Vol 21 (9) ◽  
pp. 1359-1366 ◽  
Author(s):  
John L Fowlkes ◽  
Kathryn M Thrailkill ◽  
Lichu Liu ◽  
Elizabeth C Wahl ◽  
Robert C Bunn ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Formation ◽  
De Novo ◽  
Local Administration ◽  
Aged Mouse ◽  
Igf I ◽  
Systemic And Local Administration

scholarly journals Novel mouse model of spinal cord injury-induced heterotopic ossification

2014 ◽  
Vol 51 (7) ◽  
pp. 1109-1118 ◽  
Author(s):  
Heejae Kang ◽  
Alexis B. C. Dang ◽  
Sunil K. Joshi ◽  
Bernard Halloran ◽  
Robert Nissenson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Mouse Model ◽  
Heterotopic Ossification ◽  
Cord Injury

scholarly journals Inhibition of Hif1α prevents both trauma-induced and genetic heterotopic ossification

2015 ◽  
Vol 113 (3) ◽  
pp. E338-E347 ◽  
Author(s):  
Shailesh Agarwal ◽  
Shawn Loder ◽  
Cameron Brownley ◽  
David Cholok ◽  
Laura Mangiavini ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Bone Formation ◽  
Heterotopic Ossification ◽  
De Novo ◽  
Hypoxia Inducible Factor ◽  
Lineage Tracing ◽  
Mechanical Trauma ◽  
Adaptation To Hypoxia ◽  
Type I ◽  
Pharmacologic Inhibition

Pathologic extraskeletal bone formation, or heterotopic ossification (HO), occurs following mechanical trauma, burns, orthopedic operations, and in patients with hyperactivating mutations of the type I bone morphogenetic protein receptor ACVR1 (Activin type 1 receptor). Extraskeletal bone forms through an endochondral process with a cartilage intermediary prompting the hypothesis that hypoxic signaling present during cartilage formation drives HO development and that HO precursor cells derive from a mesenchymal lineage as defined by Paired related homeobox 1 (Prx). Here we demonstrate that Hypoxia inducible factor-1α (Hif1α), a key mediator of cellular adaptation to hypoxia, is highly expressed and active in three separate mouse models: trauma-induced, genetic, and a hybrid model of genetic and trauma-induced HO. In each of these models, Hif1α expression coincides with the expression of master transcription factor of cartilage, Sox9 [(sex determining region Y)-box 9]. Pharmacologic inhibition of Hif1α using PX-478 or rapamycin significantly decreased or inhibited extraskeletal bone formation. Importantly, de novo soft-tissue HO was eliminated or significantly diminished in treated mice. Lineage-tracing mice demonstrate that cells forming HO belong to the Prx lineage. Burn/tenotomy performed in lineage-specific Hif1α knockout mice (Prx-Cre/Hif1αfl:fl) resulted in substantially decreased HO, and again lack of de novo soft-tissue HO. Genetic loss of Hif1α in mesenchymal cells marked by Prx-cre prevents the formation of the mesenchymal condensations as shown by routine histology and immunostaining for Sox9 and PDGFRα. Pharmacologic inhibition of Hif1α had a similar effect on mesenchymal condensation development. Our findings indicate that Hif1α represents a promising target to prevent and treat pathologic extraskeletal bone.

Sign in / Sign up

Export Citation Format

Share Document