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Bone Jun 2024We and others have seen that osteocytes sense high-impact osteogenic mechanical loading via transient plasma membrane disruptions (PMDs) which initiate downstream...
We and others have seen that osteocytes sense high-impact osteogenic mechanical loading via transient plasma membrane disruptions (PMDs) which initiate downstream mechanotransduction. However, a PMD must be repaired for the cell to survive this wounding event. Previous work suggested that the protein Prkd1 (also known as PKCμ) may be a critical component of this PMD repair process, but the specific role of Prkd1 in osteocyte mechanobiology had not yet been tested. We treated MLO-Y4 osteocytes with Prkd1 inhibitors (Go6976, kbNB 142-70, staurosporine) and generated an osteocyte-targeted (Dmp1-Cre) Prkd1 conditional knockout (CKO) mouse. PMD repair rate was measured via laser wounding and FM1-43 dye uptake, PMD formation and post-wounding survival were assessed via fluid flow shear stress (50 dyn/cm), and in vitro osteocyte mechanotransduction was assessed via measurement of calcium signaling. To test the role of osteocyte Prkd1 in vivo, Prkd1 CKO and their wildtype (WT) littermates were subjected to 2 weeks of unilateral axial tibial loading and loading-induced changes in cortical bone mineral density, geometry, and formation were measured. Prkd1 inhibition or genetic deletion slowed osteocyte PMD repair rate and impaired post-wounding cell survival. These effects could largely be rescued by treating osteocytes with the FDA-approved synthetic copolymer Poloxamer 188 (P188), which was previously shown to facilitate membrane resealing and improve efficiency in the repair rate of PMD in skeletal muscle myocytes. In vivo, while both WT and Prkd1 CKO mice demonstrated anabolic responses to tibial loading, the magnitude of loading-induced increases in tibial BMD, cortical thickness, and periosteal mineralizing surface were blunted in Prkd1 CKO as compared to WT mice. Prkd1 CKO mice also tended to show a smaller relative difference in the number of osteocyte PMD in loaded limbs and showed greater lacunar vacancy, suggestive of impaired post-wounding osteocyte survival. While P188 treatment rescued loading-induced increases in BMD in the Prkd1 CKO mice, it surprisingly further suppressed loading-induced increases in cortical bone thickness and cortical bone formation. Taken together, these data suggest that Prkd1 may play a pivotal role in the regulation and repair of the PMD response in osteocytes and support the idea that PMD repair processes can be pharmacologically targeted to modulate downstream responses, but suggest limited utility of PMD repair-promoting P188 in improving bone anabolic responses to loading.
PubMed: 38866124
DOI: 10.1016/j.bone.2024.117147 -
Archives of Osteoporosis Jun 2024Muscular fitness plays a major role in bone health and body composition in overweight and obese children. It is key that the development of this muscle fitness is...
UNLABELLED
Muscular fitness plays a major role in bone health and body composition in overweight and obese children. It is key that the development of this muscle fitness is affected by absolute isometric strength and dynamic strength.
PURPOSE
To compare bone health and body composition between overweight/obese children considering muscular fitness (MF) levels, and to investigate whether weight-bearing dynamic or absolute isometric strength, both involved in the development of this muscular fitness, are more related with bone health.
METHODS
MF of 59 overweight or obese children (10.1 ± 0.9 years, 27 females) was measured by a countermovement jump (CMJ), handgrip, and maximal isometric strength of knee extension. Participants were divided into four groups depending on their MF level performing a cluster analysis: 16 children with high MF (HMF) in all tests, 18 with high performance in isometric strength (HIS), 15 with high performance in CMJ (HCMJ) and 10 low isometric and low dynamic force values (LMF). Body composition values were measured by dual energy X-ray absorptiometry, and bone strength values were assessed by peripheral quantitative computed tomography. Motor skills were evaluated using TGMD-3. Multivariate analysis of covariance test was applied to analyse bone strength differences between children in the different MF groups, using maturity offset, height and weight as covariates, and correlations were investigated.
RESULTS
HMF excelled in bone health. HIS had higher cortical bone area, periosteal circumference, bone mass, polar strength strain index and fracture load than LMF, while HCMJ only showed better results in trabecular bone area than LMF. HMF had significantly better values of fracture load and periosteal and endosteal circumferences than HCMJ, but not than HIS.
CONCLUSIONS
High MF level shows positive effects on bone health in overweight/obese children. Those with highest isometric strength had better bone health compared to those with higher dynamic strength.
TRIAL REGISTRATION
The research project was registered in a public database Clinicaltrials.gov in June 2020 with the identification number NCT04418713.
Topics: Humans; Male; Child; Female; Body Composition; Muscle Strength; Bone Density; Pediatric Obesity; Physical Fitness; Overweight; Absorptiometry, Photon; Hand Strength
PubMed: 38856950
DOI: 10.1007/s11657-024-01405-3 -
Operative Neurosurgery (Hagerstown, Md.) Jun 2024Chordomas can be treated surgically, with radiotherapy, and more recently, chemotherapy.1,2 A 22-year-old female patient presented with recurrence of a clival chordoma,...
Chordomas can be treated surgically, with radiotherapy, and more recently, chemotherapy.1,2 A 22-year-old female patient presented with recurrence of a clival chordoma, after subtotal resection at an outside institution 3 months prior. MRI showed a predominantly midline lesion at the craniocervical junction with significant lateral extension eccentric to the left. A 3-staged operation was planned. A redo-endoscopic endonasal transclival transodontoid approach3-5 was used to resect the midline component, followed by an extreme lateral transcondylar transodontoid approach with transposition of the ipsilateral vertebral artery followed by drilling of the ipsilateral occipital condyle and C1 lateral mass to resect the lateral component, followed by occiput to C3 fusion given the induced craniocervical instability. Careful subperiosteal dissection with preservation of the periosteal sheath overlying the vertebral artery was performed. There was no overt evidence of vertebral artery injury intraoperatively or on immediate postoperative imaging. However, 3 weeks later, the patient presented with blood from the oral/nasal cavity. Computed tomography angiography showed an unexpected left vertebral artery pseudoaneurysm. Pseudoaneurysms can develop after microtears in the muscularis layer.6-8 Management is based on size, location, and vertebral artery dominance.9,10 This pseudoaneurysm was coiled. Postcoiling, the patient had left hypoglossal palsy. We demonstrate the step-by-step technique of an extreme lateral transcondylar transodontoid approach for a clival chordoma and the unfortunate complication of a vertebral artery pseudoaneurysm with discussion of its etiology and management options for this potentially devastating complication. The patient consented to the procedure/publication. Institutional Review Board approval not obtained as the patient was deidentified, and no additional risk is posed by the publication of this video.
PubMed: 38851871
DOI: 10.1227/ons.0000000000001221 -
European Journal of Radiology Jul 2024To assess the accuracy of 0.55 T MRI in diagnosing periprosthetic joint infection (PJI) in patients with symptomatic total hip arthroplasty (THA).
PURPOSE
To assess the accuracy of 0.55 T MRI in diagnosing periprosthetic joint infection (PJI) in patients with symptomatic total hip arthroplasty (THA).
MATERIAL AND METHODS
0.55 T MRI of patients with THA PJI (Group A) and noninfected THA (Group B), including aseptic loosening (Group C, subgroup of B) performed between May 2021 and July 2023 were analysed retrospectively. Two musculoskeletal fellowship-trained radiologists independently identified MRI bone and soft tissue changes including: marrow oedema, periosteal reaction, osteolysis, joint effusion, capsule oedema and thickening, fluid collections, muscle oedema, bursitis, inguinal adenopathy, and muscle tears. The diagnostic performance of MRI discriminators of PJI was evaluated using Fisher's exact test (p < 0.05) and interrater reliability was determined. 61 MRI scans from 60 THA patients (34 female, median age 68, range 41-93 years) in Group A (n = 9; female 4; median age 69, range 56-82 years), B (n = 51; 30; 67.5, 41-93 years), and C (10; 6; 67; 41-82 years) were included.
RESULTS
Capsule oedema (sensitivity 89 %, specificity 92 %,), intramuscular oedema (89 %, 82 %) and joint effusion (89 %, 73 %) were the best performing discriminators for PJI diagnosis (p ≤ 0.001), when viewed individually and had combined 70 % sensitivity and 100 % specificity for PJI diagnosis in parallel testing. For the differentiation between PJI and aseptic loosening, intramuscular oedema (89 %, 80 %) and capsule oedema (89 %, 80 %) were significant discriminators (p ≤ 0.001) with combined 64 % sensitivity and 96 % specificity for PJI.
CONCLUSIONS
New generation 0.55 T MRI may aid in the detection of PJI in symptomatic patients. Oedema of the joint capsule, adjacent muscles as well as joint effusion were indicative of the presence of PJI.
Topics: Humans; Female; Male; Aged; Magnetic Resonance Imaging; Prosthesis-Related Infections; Middle Aged; Aged, 80 and over; Adult; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Arthroplasty, Replacement, Hip; Hip Prosthesis; Hip Joint
PubMed: 38851014
DOI: 10.1016/j.ejrad.2024.111524 -
European Journal of Medical Research Jun 2024Conventional radiography is regularly used to evaluate complications after total hip arthroplasty. In various recent consensus meetings, however, plain radiographs of a... (Review)
Review
Conventional radiography is regularly used to evaluate complications after total hip arthroplasty. In various recent consensus meetings, however, plain radiographs of a potentially infected hip joint have been judged as being only relevant to exclude diagnoses other than infection. Solid data on radiographic presentations of periprosthetic joint infection (PJI) are scarce. As a result, the prognostic value of radiological features in low-grade PJI remains uncertain. The present review article aims to present an overview of the available literature and to develop ideas on future perspectives to define the diagnostic possibilities of radiography in PJIs of the hip. The primary outcome of interest of this systematic review was the radiologic presentation of periprosthetic joint infections of the hip. As secondary outcome of interest served the sensitivity and specificity of the radiologic presentation of periprosthetic joint infections. Of the included articles, 26 were reviews, essays, or case reports and only 18 were clinical studies. Typical radiologic abnormalities of PJI were a periosteal reaction, a wide band of radiolucency at the cement-bone or metal-bone interface, patchy osteolysis, implant loosening, bone resorption around the implant, and transcortical sinus tracts. The frequency of their occurrence is still inadequately defined. A deeper understanding of the underlying causes and the relation between microorganisms to radiologic abnormalities can probably help clinicians in the future to diagnose a PJI. This is why further research shall focus on the radiographic features of PJI.
Topics: Humans; Prosthesis-Related Infections; Prognosis; Arthroplasty, Replacement, Hip; Radiography; Hip Joint; Hip Prosthesis
PubMed: 38849967
DOI: 10.1186/s40001-024-01891-8 -
JBJS Case Connector Apr 2024We report a case of an intramuscular thigh hemangioma in a 19-year-old woman with a several year history of atraumatic thigh pain. Radiographs obtained by her primary...
CASE
We report a case of an intramuscular thigh hemangioma in a 19-year-old woman with a several year history of atraumatic thigh pain. Radiographs obtained by her primary care physician demonstrated periosteal bone reaction, prompting referral to Orthopaedic Oncology department. The patient had successful symptomatic management with propranolol.
CONCLUSION
The case highlights the diagnosis and potential treatments. In a stepwise approach to care for symptomatic benign vascular lesions, propranolol has been a proven therapeutic option and may be a useful first-line therapy for symptomatic hemangiomas.
Topics: Humans; Female; Thigh; Hemangioma; Young Adult; Muscle Neoplasms; Propranolol; Radiography; Adrenergic beta-Antagonists
PubMed: 38848412
DOI: 10.2106/JBJS.CC.24.00060 -
Restorative Dentistry & Endodontics May 2024Chronic osteomyelitis with proliferative periostitis, known as Garre's osteomyelitis, is a type of osteomyelitis characterized by a distinctive gross thickening of the...
Chronic osteomyelitis with proliferative periostitis, known as Garre's osteomyelitis, is a type of osteomyelitis characterized by a distinctive gross thickening of the periosteum of bones. Peripheral reactive bone formation can be caused by mild irritation or infection. Garre's osteomyelitis is usually diagnosed in children and young adults, and the mandible is more affected than the maxilla. The following is a case report of a 12-year-old female patient with Garre's osteomyelitis of the mandible due to an infection of a root canal-treated tooth. Without surgical intervention, the patient's symptoms were relieved through nonsurgical root canal re-treatment with long-term calcium hydroxide placement. A cone-beam computed tomography image obtained 6 months after treatment completion displayed complete healing of the periapical lesion and resolution of the peripheral reactive buccal bone. Due to the clinical features of Garre's osteomyelitis, which is characterized by thickening of the periosteum, it can be mistaken for other diseases such as fibrous dysplasia. It is important to correctly diagnose Garre's osteomyelitis based on its distinctive clinical features to avoid unnecessary surgical intervention, and it can lead to minimally invasive treatment options.
PubMed: 38841385
DOI: 10.5395/rde.2024.49.e13 -
Cellular & Molecular Immunology Jul 2024The hallmarks of spondyloarthritis (SpA) are type 3 immunity-driven inflammation and new bone formation (NBF). Macrophage migration inhibitory factor (MIF) was found to...
The hallmarks of spondyloarthritis (SpA) are type 3 immunity-driven inflammation and new bone formation (NBF). Macrophage migration inhibitory factor (MIF) was found to be a key driver of the pathogenesis of SpA by amplifying type 3 immunity, yet MIF-interacting molecules and networks remain elusive. Herein, we identified hypoxia-inducible factor-1 alpha (HIF1A) as an interacting partner molecule of MIF that drives SpA pathologies, including inflammation and NBF. HIF1A expression was increased in the joint tissues and synovial fluid of SpA patients and curdlan-injected SKG (curdlan-SKG) mice compared to the respective controls. Under hypoxic conditions in which HIF1A was stabilized, human and mouse neutrophils exhibited substantially increased expression of MIF and IL-23, an upstream type 3 immunity-related cytokine. Similar to MIF, systemic overexpression of IL-23 induced SpA pathology in SKG mice, while the injection of a HIF1A-selective inhibitor (PX-478) into curdlan-SKG mice prevented or attenuated SpA pathology, as indicated by a marked reduction in the expression of MIF and IL-23. Furthermore, genetic deletion of MIF or HIF1A inhibition with PX-478 in IL-23-overexpressing SKG mice did not induce evident arthritis or NBF, despite the presence of psoriasis-like dermatitis and blepharitis. We also found that MIF- and IL-23-expressing neutrophils infiltrated areas of the NBF in curdlan-SKG mice. These neutrophils potentially increased chondrogenesis and cell proliferation via the upregulation of STAT3 in periosteal cells and ligamental cells during endochondral ossification. Together, these results provide supporting evidence for an MIF/HIF1A regulatory network, and inhibition of HIF1A may be a novel therapeutic approach for SpA by suppressing type 3 immunity-mediated inflammation and NBF.
Topics: Animals; Macrophage Migration-Inhibitory Factors; Hypoxia-Inducible Factor 1, alpha Subunit; Disease Models, Animal; Neutrophils; Humans; Mice; Chondrogenesis; Spondylarthritis; Intramolecular Oxidoreductases; Interleukin-23; beta-Glucans; Mice, Inbred C57BL; Male; Female; Immunity
PubMed: 38839914
DOI: 10.1038/s41423-024-01183-5 -
Stem Cell Reviews and Reports Jun 2024Cell surface marker expression is one of the criteria for defining human mesenchymal stem or stromal cells (MSC) in vitro. However, it is unclear if expression of...
Cell surface marker expression is one of the criteria for defining human mesenchymal stem or stromal cells (MSC) in vitro. However, it is unclear if expression of markers including CD73 and CD90 reflects the in vivo origin of cultured cells. We evaluated expression of 15 putative MSC markers in primary cultured cells from periosteum and cartilage to determine whether expression of these markers reflects either the differentiation state of cultured cells or the self-renewal of in vivo populations. Cultured cells had universal and consistent expression of various putative stem cell markers including > 95% expression CD73, CD90 and PDPN in both periosteal and cartilage cultures. Altering the culture surface with extracellular matrix coatings had minimal effect on cell surface marker expression. Osteogenic differentiation led to loss of CD106 and CD146 expression, however CD73 and CD90 were retained in > 90% of cells. We sorted freshly isolated periosteal populations capable of CFU-F formation on the basis of CD90 expression in combination with CD34, CD73 and CD26. All primary cultures universally expressed CD73 and CD90 and lacked CD34, irrespective of the expression of these markers ex vivo indicating phenotypic convergence in vitro. We conclude that markers including CD73 and CD90 are acquired in vitro in most 'mesenchymal' cells capable of expansion. Overall, we demonstrate that in vitro expression of many cell surface markers in plastic-adherent cultures is unrelated to their expression prior to culture.
PubMed: 38837115
DOI: 10.1007/s12015-024-10743-1 -
Anticancer Research Jun 2024The increasing incidence of renal cell carcinoma (RCC) and its associated bone metastasis pose challenges in surgical interventions, warranting the exploration of novel...
BACKGROUND/AIM
The increasing incidence of renal cell carcinoma (RCC) and its associated bone metastasis pose challenges in surgical interventions, warranting the exploration of novel therapeutic approaches. Therefore, this study aimed to assess the impact of hematogenously administering acridine orange (AO) alone and in combination with zoledronic acid (ZA) on bone metastasis in RCC.
MATERIALS AND METHODS
RENCA cells (1.0×10 cells/10 μl) were directly injected into the right femur of male BALB/c mice. The mice were categorized into four groups based on the applied therapeutic intervention and were euthanized after five weeks. Micro-computed tomography was performed to quantify the extent of periosteal reaction, indicative of bone metastasis, along the entire length of the femur. Tumor weight and volume were measured at euthanization. Hematoxylin and eosin staining was used to examine the extent of tumor development in the bone. Apoptotic cell, osteoclast, and vascular endothelial growth factor (VEGF)-positive cell counts were assessed using TdT-mediated dUTP-biotin nick end labeling, tartrate-resistant acid phosphatase staining, and VEGF staining, respectively.
RESULTS
The periosteal reaction was significantly reduced in the intervention groups compared to the control group (p<0.05). The apoptotic cell numbers in the intervention groups surpassed that in the control group (p<0.05), whereas those of osteoclasts and VEGF-positive cells in the intervention groups were lower than those in the control group (p<0.05).
CONCLUSION
AO hinders bone metastasis progression in RCC, and combination therapy with ZA may be more effective than AO administration alone.
Topics: Zoledronic Acid; Animals; Carcinoma, Renal Cell; Bone Neoplasms; Kidney Neoplasms; Male; Acridine Orange; Mice; Mice, Inbred BALB C; Apoptosis; Cell Line, Tumor; Humans; Vascular Endothelial Growth Factor A; Imidazoles; X-Ray Microtomography; Xenograft Model Antitumor Assays
PubMed: 38821618
DOI: 10.21873/anticanres.17055