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FASEB Journal : Official Publication of... Jun 2023Achilles tendon rupture is a common debilitating medical condition. The healing process is slow and can be affected by heterotopic ossification (HO), which occurs when... (Review)
Review
Achilles tendon rupture is a common debilitating medical condition. The healing process is slow and can be affected by heterotopic ossification (HO), which occurs when pathologic bone-like tissue is deposited instead of the soft collagenous tendon tissue. Little is known about the temporal and spatial progression of HO during Achilles tendon healing. In this study we characterize HO deposition, microstructure, and location at different stages of healing in a rat model. We use phase contrast-enhanced synchrotron microtomography, a state-of-the-art technique that allows 3D imaging at high-resolution of soft biological tissues without invasive or time-consuming sample preparation. The results increase our understanding of HO deposition, from the early inflammatory phase of tendon healing, by showing that the deposition is initiated as early as one week after injury in the distal stump and mostly growing on preinjury HO deposits. Later, more deposits form first in the stumps and then all over the tendon callus, merging into large, calcified structures, which occupy up to 10% of the tendon volume. The HOs were characterized by a looser connective trabecular-like structure and a proteoglycan-rich matrix containing chondrocyte-like cells with lacunae. The study shows the potential of 3D imaging at high-resolution by phase-contrast tomography to better understand ossification in healing tendons.
Topics: Animals; Rats; Achilles Tendon; Wound Healing; Osteogenesis; Bone and Bones; Ossification, Heterotopic
PubMed: 37219456
DOI: 10.1096/fj.202201018RRR -
Cells Nov 2021Retinoids are metabolic derivatives of vitamin A and regulate the function of many tissues and organs both prenatally and postnatally. Active retinoids, such as... (Review)
Review
Retinoids are metabolic derivatives of vitamin A and regulate the function of many tissues and organs both prenatally and postnatally. Active retinoids, such as -retinoic acid, are produced in the cytoplasm and then interact with nuclear retinoic acid receptors (RARs) to up-regulate the transcription of target genes. The RARs can also interact with target gene response elements in the absence of retinoids and exert a transcriptional repression function. Studies from several labs, including ours, showed that chondrogenic cell differentiation and cartilage maturation require (i) the absence of retinoid signaling and (ii) the repression function by unliganded RARs. These and related insights led to the proposition that synthetic retinoid agonists could thus represent pharmacological agents to inhibit heterotopic ossification (HO), a process that recapitulates developmental skeletogenesis and involves chondrogenesis, cartilage maturation, and endochondral ossification. One form of HO is acquired and is caused by injury, and another severe and often fatal form of it is genetic and occurs in patients with fibrodysplasia ossificans progressiva (FOP). Mouse models of FOP bearing mutant ACVR1R206H, characteristic of most FOP patients, were used to test the ability of the retinoid agonists selective for RARα and RARγ against spontaneous and injury-induced HO. The RARγ agonists were found to be most effective, and one such compound, palovarotene, was selected for testing in FOP patients. The safety and effectiveness data from recent and ongoing phase II and phase III clinical trials support the notion that palovarotene may represent a disease-modifying treatment for patients with FOP. The post hoc analyses showed substantial efficacy but also revealed side effects and complications, including premature growth plate closure in some patients. Skeletally immature patients will need to be carefully weighed in any future regulatory indications of palovarotene as an important therapeutic option in FOP.
Topics: Animals; Chondrogenesis; Clinical Trials as Topic; Humans; Ossification, Heterotopic; Receptors, Retinoic Acid; Retinoids; Signal Transduction
PubMed: 34831466
DOI: 10.3390/cells10113245 -
Stem Cells Translational Medicine Nov 2022Heterotopic ossification (HO) is a dynamic, complex pathologic process that often occurs after severe polytrauma trauma, resulting in an abnormal mesenchymal stem cell...
Heterotopic ossification (HO) is a dynamic, complex pathologic process that often occurs after severe polytrauma trauma, resulting in an abnormal mesenchymal stem cell differentiation leading to ectopic bone growth in soft-tissues including tendons, ligaments, and muscles. The abnormal bone structure and location induce pain and loss of mobility. Recently, we observed that NGF (Nerve growth factor)-responsive TrkA (Tropomyosin receptor kinase A)-expressing nerves invade sites of soft-tissue trauma, and this is a necessary feature for heterotopic bone formation at sites of injury. Here, we assayed the effects of the partial TrkA agonist Gambogic amide (GA) in peritendinous heterotopic bone after extremity trauma. Mice underwent HO induction using the burn/tenotomy model with or without systemic treatment with GA, followed by an examination of the injury site via radiographic imaging, histology, and immunohistochemistry. Single-cell RNA Sequencing confirmed an increase in neurotrophin signaling activity after HO-inducing extremity trauma. Next, TrkA agonism led to injury site hyper-innervation, more brisk expression of cartilage antigens within the injured tendon, and a shift from FGF to TGFβ signaling activity among injury site cells. Nine weeks after injury, this culminated in higher overall levels of heterotopic bone among GA-treated animals. In summary, these studies further link injury site hyper-innervation with increased vascular ingrowth and ultimately heterotopic bone after trauma. In the future, modulation of TrkA signaling may represent a potent means to prevent the trauma-induced heterotopic bone formation and improve tissue regeneration.
Topics: Mice; Animals; Disease Models, Animal; Ossification, Heterotopic; Tenotomy; Burns; Neurons; Osteogenesis
PubMed: 36222619
DOI: 10.1093/stcltm/szac073 -
The Journal of the American Academy of... Jun 2022Ossification of the ligamentum flavum (OLF) is an uncommon but potentially serious spinal condition which can cause progressive compression of the spinal canal with...
Ossification of the ligamentum flavum (OLF) is an uncommon but potentially serious spinal condition which can cause progressive compression of the spinal canal with associated devastating neurologic compromise. Although debate exists regarding the exact etiology of OLF, overexpression of genes and transcription factors centered around the Notch and Wnt signaling pathways because of increased mechanical stress seems to be related. There are many clinical and radiographic presentations of OLF; however, progressive myelopathy is the most commonly encountered. Radiographic analysis may reveal isolated OLF or OLF combined with ossification of other areas of the spine, such as disk, posterior longitudinal ligament, and dura. When surgery is necessary for OLF, several surgical strategies exist including open laminectomy with excision, endoscopic decompression, Bridge Crane resection, en block resection, and combined anterior and posterior approaches. Resection may be complicated by dural adhesion or dural ossification, and postoperative neurologic deficits are not uncommon.
Topics: Decompression, Surgical; Humans; Laminectomy; Ligamentum Flavum; Lumbar Vertebrae; Ossification, Heterotopic; Osteogenesis; Retrospective Studies; Thoracic Vertebrae; Treatment Outcome
PubMed: 35298441
DOI: 10.5435/JAAOS-D-21-01253 -
Annals of Plastic Surgery Apr 2022Heterotopic ossification (HO) is a known complication of burns. The incidence of this complication is low. The etiology is unclear, but experiment conducted about HO can...
Heterotopic ossification (HO) is a known complication of burns. The incidence of this complication is low. The etiology is unclear, but experiment conducted about HO can be significant. Currently, there are still no targeted, effective preventive and therapeutic measures against it. In this study, the relevant literature is summarized to demonstrate the potential pathogenic mechanisms, diagnosis, prophylaxis, and treatment measures of HO in burn patients. Early diagnosis and treatment can be effective in improving the prognosis of patients.
Topics: Burns; Early Diagnosis; Humans; Ossification, Heterotopic; Prognosis
PubMed: 34270474
DOI: 10.1097/SAP.0000000000002901 -
Minerva Dental and Oral Science Apr 2024Ossification disorders can affect the stylohyoid ligament as well the stylomandibular ligament. The symptomathology between those syndromes and other pathologies it has... (Review)
Review
INTRODUCTION
Ossification disorders can affect the stylohyoid ligament as well the stylomandibular ligament. The symptomathology between those syndromes and other pathologies it has been a problem because there is not a guideline.
EVIDENCE ACQUISITION
With the aim to establish prevalence, diagnosis and etiopathogenesis of Eagle and Ernest syndromes, a scoping review was performed base on PRISMA criteria.
EVIDENCE SYNTHESIS
To review stylohyoid ligament and Eagle Syndrome 93 articles were selected. Three articles regarding the stylomandibular ligament and Ernest Syndrome were founded and selected.
CONCLUSIONS
Both syndromes should be clinically diagnosed and corroborate with imaging (2D or 3D), although imaging in Ernest Syndrome is not clear as well in Eagle Syndrome. A decisional algorithm for diagnosis of Eagle Syndrome and Ernest Syndrome is presented.
Topics: Humans; Ossification, Heterotopic; Ligaments, Articular; Neck; Temporal Bone; Syndrome
PubMed: 36197280
DOI: 10.23736/S2724-6329.22.04724-6 -
Molecular and Cellular Biochemistry Oct 2022Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disease caused by heterozygous missense mutations in Activin A receptor type I which is also known as... (Review)
Review
Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disease caused by heterozygous missense mutations in Activin A receptor type I which is also known as Activin-like kinase 2 (ALK2), a type I receptor of Bone Morphogenetic Proteins(BMP). Patients with FOP usually undergo episodic flare-ups and the heterotopic ossification in soft and connective tissues. Molecular mechanism study indicates that Activin A, the ligand which normally transduces Transforming Growth Factor Beta signaling, abnormally activates BMP signaling through ALK2 mutants in FOP, leading to heterotopic bone formation. To date, effective therapies to FOP are unavailable. However, significant advances have recently been made in the development of FOP drugs. In this article, we review the recent advances in understanding the FOP mechanism and drug development, with a focus on the small-molecular and antibody drugs currently in the clinical trials for FOP treatment.
Topics: Activins; Bone Morphogenetic Proteins; Drug Development; Humans; Ligands; Mutation; Myositis Ossificans; Ossification, Heterotopic; Transforming Growth Factor beta
PubMed: 35536530
DOI: 10.1007/s11010-022-04446-9 -
Journal of Orthopaedic Research :... Apr 2020In this review, we highlight themes from a recent workshop focused on "Plasticity of Cell Fate in Musculoskeletal Tissues" held at the Orthopaedic Research Society's... (Review)
Review
In this review, we highlight themes from a recent workshop focused on "Plasticity of Cell Fate in Musculoskeletal Tissues" held at the Orthopaedic Research Society's 2019 annual meeting. Experts in the field provided examples of mesenchymal cell plasticity during normal musculoskeletal development, regeneration, and disease. A thorough understanding of the biology underpinning mesenchymal cell plasticity may offer a roadmap for promoting regeneration while attenuating pathologic differentiation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:708-718, 2020.
Topics: Animals; Cell Differentiation; Cell Plasticity; Disease; Humans; Musculoskeletal Development; Myositis Ossificans; Ossification, Heterotopic; Regeneration; Wounds and Injuries
PubMed: 31721278
DOI: 10.1002/jor.24523 -
Scientific Reports Dec 2019Heterotopic Ossification (HO) is a potential long-term complication in orthopaedic surgery. It is commonly classified according to the Brooker classification, which is...
Heterotopic Ossification (HO) is a potential long-term complication in orthopaedic surgery. It is commonly classified according to the Brooker classification, which is based on radiological findings. To our knowledge the correlation of histological features to the Brooker grade is unknown as is the association between HO and the indication for revision. The aim of this paper is to analyze the ossification grade of HO tissue in patients undergoing revision hip and knee arthroplasty and to propose a histologically based classification system for HO. We also assess the relationship between the grade of HO and the indication for revision (septic and aseptic revision). From January to May 2019 we collected 50 human HO samples from hip and knee revision arthroplasty cases. These tissue samples were double-blinded and sent for histopathological diagnostic. Based on these results, we developed a classification system for the progression of HO. The grade of ossification was based on three characteristics: Grade of heterotopic ossification (Grade 1-3), presence of necrosis (N0 or N1) and the presence of osteomyelitis (HOES-Score Type 1 to 5). Demographic data as well as surgical details and indication for surgery was prospectively collected from clinical records. Fifty tissue samples were harvested from 44 hips and 6 knee joints. Of these 33 exhibited Grade I ossifications (66%), followed by 11 Grade II (22%) and one Grade III (2%). Necrosis was noted in two tissue samples (4%) and 2 more had osteomyelitis findings according to HOES-Score. Six samples (12%) with radiologically suggestive of HO turned out to be wear-induced synovitis, SLIM Type 1. Of these cases 16 were septic (32%) and 34 aseptic (68%) revisions. Most of the HO tissue samples were classified as a low-grade. High-grade ossification-Score is rare. Higher grades of ossification seem to be associated with septic revision cases. Wear-induced synovitis potentially influences HO development. A histological scoring system for ossification grading can be derived from the data presented in this study.
Topics: Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Disease Progression; Female; Hip Joint; Humans; Knee Joint; Male; Middle Aged; Necrosis; Ossification, Heterotopic; Osteomyelitis; Prospective Studies; Radiography; Severity of Illness Index; Synovitis
PubMed: 31804584
DOI: 10.1038/s41598-019-54986-2 -
Journal of ISAKOS : Joint Disorders &... Feb 2024In elbow stiffness, pre-operative assessments should identify the articular and peri-articular tissues involved and, more specifically, they should determine how...
In elbow stiffness, pre-operative assessments should identify the articular and peri-articular tissues involved and, more specifically, they should determine how preserved the articular surfaces and osteo-articular congruity are. We will focus on the most important conditions and tissue reactions after trauma in order to understand the causes of joint stiffness. A logical surgical planning is based upon a deep knowledge of the anatomical obstacles and of the associated lesions that the trauma provoked with. The peri-articular soft tissue contractures. The osteo-articular incongruity.
Topics: Humans; Elbow; Elbow Joint; Elbow Injuries; Treatment Outcome; Joint Dislocations; Arthritis; Ossification, Heterotopic
PubMed: 37879605
DOI: 10.1016/j.jisako.2023.10.009