scholarly journals βig-h3 enhances chondrogenesis via promoting mesenchymal condensation in rat Achilles tendon heterotopic ossification model

Aging ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 7030-7041 ◽  
Author(s):  
Qiang Zhang ◽  
Yan Zhang ◽  
Meijun Yan ◽  
Kai Zhu ◽  
Qihang Su ◽  
...  
Keyword(s):  
Achilles Tendon ◽  
Heterotopic Ossification ◽  
Mesenchymal Condensation

scholarly journals Heterotopic Ossification After an Achilles Tendon Rupture Cannot Be Prevented by Early Functional Rehabilitation

2020 ◽  
Vol 478 (5) ◽  
pp. 1101-1108 ◽  
Author(s):  
S. Peter Magnusson ◽  
Anne-Sofie Agergaard ◽  
Christian Couppé ◽  
René B. Svensson ◽  
Susan Warming ◽  
...  
Keyword(s):  
Achilles Tendon ◽  
Heterotopic Ossification ◽  
Tendon Rupture ◽  
Achilles Tendon Rupture ◽  
Functional Rehabilitation

scholarly journals Microarchitecture of Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva: An HR-pQCT Case Series

2021 ◽  
Vol 9 ◽  
Author(s):  
Esmée Botman ◽  
Melissa S. A. M. Bevers ◽  
Caroline E. Wyers ◽  
Bert van Rietbergen ◽  
Bernd P. Teunissen ◽  
...  
Keyword(s):  
Achilles Tendon ◽  
Trabecular Bone ◽  
Heterotopic Ossification ◽  
Cortical Thickness ◽  
Volume Fraction ◽  
Bone Volume ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Trabecular Bone Volume ◽  
Bone Volume Fraction ◽  
Skeletal Bone

It is challenging to study heterotopic ossification (HO) in patients with fibrodysplasia ossificans progressiva (FOP) due to the contraindication of invasive techniques (i.e., bone biopsies), which can trigger flare-ups. The aim of this case study was to assess mature HO at the microarchitectural level non-invasively with high-resolution peripheral quantitative computed tomography (HR-pQCT). Depending on the patient’s mobility, HR-pQCT scans were acquired of peripherally located HO and standard distal radius and tibia regions in two FOP patients, a 33-year-old woman and a 23-year-old man, with the classical mutation (p.R206H). HO was located around the halluces, the ankles, and in the Achilles tendon. Standard HR-pQCT analyses were performed of the distal radius, tibia, and HO to quantify bone mineral density (BMD) and bone microarchitecture. Micro-finite element analysis was used to estimate failure load (FL). The outcomes were compared between HO and neighboring skeletal bone and with an age- and gender-matched normative dataset from literature. The bone parameters of the radius were within the interquartile range (IQR) of normative data. In contrast, in the tibiae of both patients, total and trabecular BMD were below the IQR, as were trabecular bone volume fraction, number, and thickness, cortical thickness, and FL. Trabecular separation and heterogeneity were above the IQR. Isolated HO in the Achilles tendon had a lower total, trabecular, and cortical BMD, trabecular bone volume fraction, and cortical thickness than the normative tibia data. Trabecular microarchitecture was within the IQR, and FL was approximately 10% higher than that of the neighboring tibia after accounting for areal differences. Other scanned HO could only be qualitatively assessed, which revealed coalescence with the neighboring skeletal bone, development of a neo-cortex, and partial replacement of the original skeletal cortex with trabeculae. To conclude, isolated HO seemed microarchitecturally more comparable to reference tibia data than the peripheral skeleton of the FOP patients. HO and skeleton also appear to be able to become one entity when contiguous.

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.

scholarly journals BRD4 promotes heterotopic ossification through upregulation of LncRNA MANCR

2021 ◽  
Vol 10 (10) ◽  
pp. 668-676
Author(s):  
Lei Liu ◽  
ZiHao Li ◽  
Siwen Chen ◽  
Haowen Cui ◽  
Xiang Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Achilles Tendon ◽  
Heterotopic Ossification ◽  
Soft Tissues ◽  
Quantitative Polymerase Chain Reaction ◽  
Gradient Centrifugation ◽  
Alizarin Red

Aims Acquired heterotopic ossification (HO) is a debilitating disease characterized by abnormal extraskeletal bone formation within soft-tissues after injury. The exact pathogenesis of HO remains unknown. It was reported that BRD4 may contribute to osteoblastic differentiation. The current study aims to determine the role of BRD4 in the pathogenesis of HO and whether it could be a potential target for HO therapy. Methods Achilles tendon puncture (ATP) mouse model was performed on ten-week-old male C57BL/6J mice. One week after ATP procedure, the mice were given different treatments (e.g. JQ1, shMancr). Achilles tendon samples were collected five weeks after treatment for RNA-seq and real-time quantitative polymerase chain reaction (RT-qPCR) analysis; the legs were removed for micro-CT imaging and subsequent histology. Human bone marrow mesenchymal stem cells (hBMSCs) were isolated and purified bone marrow collected during surgeries by using density gradient centrifugation. After a series of interventions such as knockdown or overexpressing BRD4, Alizarin red staining, RT-qPCR, and Western Blot (Runx2, alkaline phosphatase (ALP), Osx) were performed on hBMSCs. Results Overexpression of BRD4 enhanced while inhibition of Brd4 suppressed the osteogenic differentiation of hBMSCs in vitro. Overexpression of Brd4 increased the expression of mitotically associated long non-coding RNA (Mancr). Downregulation of Mancr suppressed the osteoinductive effect of BRD4. In vivo, inhibition of BRD4 by JQ1 significantly attenuated pathological bone formation in the ATP model (p = 0.001). Conclusion BRD4 was found to be upregulated in HO and Brd4-Mancr-Runx2 signalling was involved in the modulation of new bone formation in HO. Cite this article: Bone Joint Res 2021;10(10):668–676.

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.

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