scholarly journals Role of the P2X7 Receptor in the Osteogenesis of Heterotopic Ossification of the Achilles Tendon

2022 ◽  
Author(s):  
Shi Cheng ◽  
Siqi Zhang ◽  
Jinglong Yan ◽  
Songcen Lv
Keyword(s):  
Stem Cells ◽  
Bone Formation ◽  
Achilles Tendon ◽  
Heterotopic Ossification ◽  
P2x7 Receptor ◽  
Control Group ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Ectopic Ossification ◽  
Inflammatory Conditions

Abstract Background Heterotopic ossification (HO) refers to a painful and complex disease. HO occurs in the setting of persistent systemic inflammation and appears in flare-ups during inflammation, following injury. In the recent research, the P2X7 receptor (P2X7R) is tightly involved in the osteogenesis of periodontal ligament stem cells under the inflammatory conditions. The ionotropic P2X7 receptor (P2X7R) is an ATP-gated ion channel expressed in the majority of stem cells. However, the function of P2X7R in the pathological formation of HO is unclear. Here, this paper hypothesizes that in the model of Achilles tendon ectopic ossification, P2X7R is overexpressed in tendon-derived stem cells and promote osteogenesis of tendon-derived stem cells under inflammatory conditions. Methods The tenotomy puncture and burn injury-induced HO model was constructed. The qPCR and immunofluorescence were used to detect the expression of P2X7R at the site of injured Achilles tendon where HO occurs. Achilles tendon stem cells (SCs) from control group and experimental group sources were cultivated separately under inflammatory conditions. The cells from the two groups were cultured for osteogenic analysis. In addition, a specific antagonist of P2X7R, BBG was used to detect whether reversed the above process. At last, BBG was used to intervene in animal models of heterotopic ossification. Results Under inflammatory conditions, P2X7R expression of the Achilles tendon and osteogenic capability of SCs is higher in heterotopic ossification group (HOG) than in other two groups. The P2X7R expression was positive correlated with the capacity of osteogenesis of SCs. BBG can inhibit osteogenic differentiation and subsequent bone formation in the P2X7R overexpress of SCs. BBG impeded the heterotopic bone formation in animal model. Conclusions P2X7R is one of the crucial mediators in the formation of the HO, blocking which may represent a potential therapeutic target for HO.

A higher expression of P2X7 receptor at the site of heterotopic ossification promotes osteogenesis

2021 ◽  
Author(s):  
Shi Cheng ◽  
Pengbin Yin ◽  
Yi Li ◽  
Ming Chen ◽  
Duanyang Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Achilles Tendon ◽  
Heterotopic Ossification ◽  
P2x7 Receptor ◽  
Complex Disease ◽  
Burn Injury ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Inflammatory Condition ◽  
Ectopic Bone

Abstract Background Heterotopic ossification (HO) refers to a painful and complex disease. Adenosine triphosphate (ATP), as a key modulator of inflammation, is verified to promote the development of HO. However, the mechanism remains to be illustrated. The ionotropic P2X7 receptor (P2X7R) is an ATP-gated ion channel expressed in the majority of stem cells. Here, this paper hypothesizes that P2X7R may be activated by extracellular ATP and promote osteogenesis of stem cells under inflammatory condition, ending up in the formation of ectopic bone. Methods The tenotomy puncture and burn injury-induced HO model was constructed. The expression of P2X7R was found increasing at the site of injured Achilles tendon where HO occurs. Mesenchymal stem cells (MSCs) were cultivated under an inflammatory condition plus Bz-ATP treatment which mimicked a microenvironment of HO site. An induction in P2X7R expression was also observed along with an enhancement of osteogenesis. In addition, an inhibition of P2X7R expression by its specific antagonist successfully reversed the above process. Results P2X7R expression of the Achilles tendon and osteogenic capability of SCs is higher in HOG than in other two groups. Bz-ATP promoted osteogenesis under inflammation condition. BBG impeded the heterotopic bone formation in animal model. Conclusions P2X7R is a crucial mediator in ATP-signaling promotion of HO, blocking which may represent a potential therapeutic target for HO.

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 Circ-FURIN Expression Enhances Osteoblast Differentiation In Dental Pulp Stem Cells Via SOX11 Signaling Pathway Sponging miR-125

2021 ◽  
Author(s):  
Fang Ji ◽  
Yueting Lin ◽  
Jing Pan ◽  
Zhao Yang ◽  
Qianhui Ren ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Formation ◽  
Signaling Pathway ◽  
Dental Pulp ◽  
Osteoblast Differentiation ◽  
Dental Pulp Stem Cells ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Downstream Target ◽  
Report Analysis

Abstract Background: Many studies have found that circRNA plays a part in osteoblast differentiation. However, its mechanism remains unknown. Methods: High-throughput sequencing was used to identifield the different expression of circRNA during osteogenic dental pulp stem cells (DPSCs) differentiation. Luciferase report analysis and RT-qPCR were used to clarify the expression and regulation relationship among circ-FURIN, miR-125 and SOX11. The heterotopic bone formation experiment was further used to confirm the osteoblast differentiation of DPSC with different expression of circ-FURIN, miR-125 and SOX11. Results: Study indicated that circ-FURIN expression remarkably increased during osteoblast differentiation, yet circ-FURIN knockdown suppressed it. Bioinformatics and luciferase results discovered that miR-125 is the downstream target of circ-FURIN. Furthermore, circ-FURIN upregulation decreased miR-125 expression. MiR-125 upregulation restored the promotion effect of circ-FURIN on osteogenic DPSC differentiation. Luciferase report analysis verified that SOX11 is miR-125 downstream target. miR-125 overexpression suppressed osteogenic DPSC differentiation through targeting SOX11. SOX11 overexpression restored miR-125 inhibitory effect on osteogenic DPSC differentiation. In vivo experiments with heterotopic bone model suggested that circ-FURIN overexpression has crucial function to enhance heterotopic bone formation. Conclusions: In summary, circ-FURIN enhances osteoblast DPSC differentiation via the SOX11 signaling pathway by sponging miR-125. These findings suggest a novel therapeutic target for osteoporosis treatment.

scholarly journals Targeting local lymphatics to ameliorate heterotopic ossification via FGFR3-BMPR1a pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dali Zhang ◽  
Junlan Huang ◽  
Xianding Sun ◽  
Hangang Chen ◽  
Shuo Huang ◽  
...  
Keyword(s):  
Bone Formation ◽  
Heterotopic Ossification ◽  
Growth Factor Receptor ◽  
Lineage Tracing ◽  
Conditional Knockout ◽  
Heterotopic Bone ◽  
Dependent Manner ◽  
Heterotopic Bone Formation ◽  
Inflammatory Microenvironment ◽  
Achilles Tenotomy

AbstractAcquired heterotopic ossification (HO) is the extraskeletal bone formation after trauma. Various mesenchymal progenitors are reported to participate in ectopic bone formation. Here we induce acquired HO in mice by Achilles tenotomy and observe that conditional knockout (cKO) of fibroblast growth factor receptor 3 (FGFR3) in Col2+ cells promote acquired HO development. Lineage tracing studies reveal that Col2+ cells adopt fate of lymphatic endothelial cells (LECs) instead of chondrocytes or osteoblasts during HO development. FGFR3 cKO in Prox1+ LECs causes even more aggravated HO formation. We further demonstrate that FGFR3 deficiency in LECs leads to decreased local lymphatic formation in a BMPR1a-pSmad1/5-dependent manner, which exacerbates inflammatory levels in the repaired tendon. Local administration of FGF9 in Matrigel inhibits heterotopic bone formation, which is dependent on FGFR3 expression in LECs. Here we uncover Col2+ lineage cells as an origin of lymphatic endothelium, which regulates local inflammatory microenvironment after trauma and thus influences HO development via FGFR3-BMPR1a pathway. Activation of FGFR3 in LECs may be a therapeutic strategy to inhibit acquired HO formation via increasing local lymphangiogenesis.

External Beam Radiation Helps Prevent Heterotopic Bone Formation in Patients With a History of Heterotopic Ossification

2006 ◽  
Vol 21 (5) ◽  
pp. 731-736 ◽  
Author(s):  
Samuel T. Chao ◽  
Shih-Yuan Lee ◽  
Lester S. Borden ◽  
Michael J. Joyce ◽  
Viktor E. Krebs ◽  
...  
Keyword(s):  
Bone Formation ◽  
Heterotopic Ossification ◽  
External Beam Radiation ◽  
Heterotopic Bone ◽  
External Beam ◽  
Heterotopic Bone Formation ◽  
Beam Radiation ◽  
History Of

scholarly journals Overexpression of bone morphogenetic protein 2 through aberrant canonical Wnt/β-catenin signaling pathway plays an important role in heterotopic ossification of adrenal myelolipoma

2014 ◽  
Vol 8 (1-2) ◽  
pp. 104 ◽  
Author(s):  
Yozo Mitsui ◽  
Hiroaki Yasumoto ◽  
Miho Hiraki ◽  
Naoko Arichi ◽  
Noriyoshi Ishikawa ◽  
...  
Keyword(s):  
Bone Formation ◽  
Heterotopic Ossification ◽  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Bone Morphogenetic Protein 2 ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Adrenal Myelolipoma ◽  
Morphogenetic Protein ◽  
Canonical Wnt

The precise mechanism of heterotopic ossification caused by several types of tumours is largely unknown. However, recent studies have indicated that bone morphogenetic protein 2 (BMP2) is closely linked to the Wnt/β-catenin signaling pathway in this rare phenomenon of bone formation. We report a rare case of adrenal myelolipoma (ML) in a 27-year-old woman with heterotopic bone formation. Immunohistochemical findings showed BMP2 expression in the cytoplasm of tumour cells, as well as the matrix adjacent to newly developed bone tissue. In addition, β-catenin was prominent in the cytoplasm and nuclei of BMP2-positive tumour cells. To the best of our knowledge, this is the first report of adrenal ML showing heterotopic ossification with accelerated expression of both BMP2 and β-catenin. Our case findings indicate that BMP2 overexpression via aberrant canonical Wnt/β-catenin signaling may contribute to heterotopic bone formation occurring in adrenal ML.

Chondrogenic pre-induction of human mesenchymal stem cells on β-TCP: Enhanced bone quality by endochondral heterotopic bone formation

2010 ◽  
Vol 6 (8) ◽  
pp. 3292-3301 ◽  
Author(s):  
Patricia Janicki ◽  
Philip Kasten ◽  
Kerstin Kleinschmidt ◽  
Reto Luginbuehl ◽  
Wiltrud Richter
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Bone Quality ◽  
Human Mesenchymal Stem Cells ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation

scholarly journals Heterotopic Ossification in Benign and Malignant Renal Neoplasms

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S151-S151
Author(s):  
S Badeti ◽  
P Q Deb ◽  
D Heller ◽  
V Fitzhugh ◽  
R Weiss
Keyword(s):  
Bone Formation ◽  
Heterotopic Ossification ◽  
Clinical Features ◽  
Renal Tumors ◽  
Renal Neoplasm ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Cystic Nephroma ◽  
Renal Neoplasms ◽  
Female Ratio

Abstract Introduction/Objective Heterotopic bone formation in renal neoplasms is a rare phenomenon. Ossification with or without marrow elements has been reported in both benign and malignant renal tumors. Due to its rarity, the epidemiological and clinical features of this finding are not well-documented. Herein, we have examined heterotopic ossification in renal neoplasms and summarized the epidemiological and clinical features of this entity. Methods/Case Report A database search on PubMed, Scopus, and Google Scholar was performed using a combination of proper search terms. Full article texts of all search results were reviewed with reference lists screened for additional articles matching the search criteria. The demographic details of the patients, disease characteristics, treatment, and outcomes were all extracted from full text articles and were summarized in a pre-standardized form. The inclusion criteria were set as any epithelial renal neoplasm with histological evidence of heterotopic ossification. A case of clear cell renal cell carcinoma (CCRCC) with heterotopic ossification diagnosed in our institution is included in the study. Results (if a Case Study enter NA) A total of 30 cases were found of renal neoplasms with bone formation. The majority of patients were between the ages of 40 to 60. The male to female ratio was 1:1. The majority (19/30) were histologically diagnosed as CCRCC, the most common subtype of kidney tumor with a few cases diagnosed as chromophobe RCC (4/30), papillary RCC (3/30), and cystic nephroma (2/30). Of the neoplasms reported, tumor size varied from 3.0 cm to 28.8 cm. Conclusion Heterotopic ossification of renal neoplasms often presents a diagnostic challenge to the radiologist as other benign conditions such as extramedullary hematopoiesis can be in the differential. The rarity of this phenomenon renders pre-surgical diagnosis difficult. Our study documents this phenomenon to be seen in a variety of renal neoplasms and underscores the necessity to be aware of this rare entity.

scholarly journals Low-grade fibromyxoid sarcoma with heterotopic bone formation: case report and review of the literature

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S25-S25
Author(s):  
S Serinelli ◽  
L Gitto ◽  
G de la Roza ◽  
D J Zaccarini ◽  
G G Mookerjee ◽  
...  
Keyword(s):  
Case Report ◽  
Bone Formation ◽  
Heterotopic Ossification ◽  
Low Grade ◽  
Heterotopic Bone ◽  
Tumor Type ◽  
Heterotopic Bone Formation ◽  
Computed Tomography Images ◽  
Fibromyxoid Sarcoma ◽  
Bone Metaplasia

Abstract Introduction/Objective Low-grade fibromyxoid sarcoma (LGFMS) is an uncommon soft tissue malignancy with deceptively bland histologic appearance, and a tendency for late recurrence and metastasis. Cases with significant heterotopic ossification are rare. This presentation aims to characterize the features of LGFMSs showing heterotopic ossification reported in the literature, and further review the morphologic spectrum of this malignant neoplasm. Methods/Case Report We report the case of a 42-year-old male presenting with a 20-year history of a painless tumor in his left upper thigh. Computed tomography images showed coarse punctate peripheral calcifications, and the mass was resected. The tumor cells were immunohistochemically positive for MUC4, and positive for FUS (16p11.2) gene rearrangement by fluorescence in situ hybridization. Lamellar and woven bone with admixed adipose tissue was seen. Immunohistochemistry also showed focal weak to moderate staining for TLE-1. An English literature search using the terms “Evans tumor”, “low-grade fibromyxoid sarcoma”, “ossification”, “osseous metaplasia”, “bone metaplasia” and “bone formation” was performed. Nine cases were identified. The majority of subjects were males, with a mean age of 38 years (range of 12-61 years). The duration of symptoms before diagnosis ranged from a few months to 10 years. The tumor size ranged from 2.5 and to more than 12 cm. In a minority of subjects, calcifications were identified on imaging studies. Histologically, bone metaplasia was mainly seen at the periphery of the tumor. The majority of cases had a chromosomal translocation (FUS-CREB3L2 in 5 cases and EWSR1-CREB3L1 in one). Results (if a Case Study enter NA) NA Conclusion LGFMS is a tumor that can occur in a wide range of anatomical sites, and should be included in the differential diagnosis of any spindle cell neoplasm with hypocellular areas and bland cytology. Pathologists and clinicians should be aware of the rare possibility of heterotopic ossification in this tumor type, which can be radiologically detected as calcification and then confirmed histopathologically.

Sign in / Sign up

Export Citation Format

Share Document