3,753 results match your criteria: "Osteopetrosis"

Fosl2 Deficiency Predisposes Mice to Osteopetrosis, Leading to Bone Marrow Failure.

J Immunol

April 2024

Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou, Fujian, China.

Arthritis causes Fos-like 2 (Fosl2) inactivation, and various immune cells contribute to its pathogenesis. However, little is known about the role of Fosl2 in hematopoiesis and the possible pathological role of Fosl2 inactivation in the hematopoietic system in arthritis. In this study, we show that Fosl2 maintains hematopoietic stem cell (HSC) quiescence and differentiation while controlling the inflammatory response via macrophages.

View Article and Find Full Text PDF
Article Synopsis
  • Osteocalcin (OC) is a key protein secreted by bone-forming cells (osteoblasts) and exists in two forms: carboxylated OC (cOC), which helps strengthen bones, and undercarboxylated OC (ucOC), which may influence various body functions.
  • The review focuses on the role of OC in conditions like diabetes, osteoporosis, and inflammatory joint diseases, highlighting findings from clinical trials.
  • It notes that lower levels of total and undercarboxylated OC are linked to type 2 diabetes risk, but total OC may not be a reliable marker for bone turnover in certain conditions like postmenopausal osteoporosis or arthritis.
View Article and Find Full Text PDF

Osteopetrosis is an uncommon and inherited disorder. Some disease-specific characteristics, such as diffuse osteosclerosis and a high incidence of fractures, may potentially affect postoperative rehabilitation. This report presents a case of successful rehabilitation early after total hip arthroplasty for osteopetrosis.

View Article and Find Full Text PDF

Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src.

Nat Commun

February 2024

Institute of Orthopedic Biomedical and Device Innovation, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.

Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity.

View Article and Find Full Text PDF

Generation of an induced pluripotent stem cell line (SYSUSCi004-A) from a patient with Infantile Malignant Osteopetrosis.

Stem Cell Res

April 2024

Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong, China; Center for Stem Cells Translational Medicine, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong, China. Electronic address:

Infantile Malignant Osteopetrosis (IMO) is a rare, severe autosomal recessive form of osteopetrosis. Here, the peripheral blood mononuclear cells (PBMCs) extracted from a patient with IMO carrying a compound heterozygous mutation in T cell immune regulator 1, ATPase H + transporting V0 subunit a3 (TCIRG1) gene (c.242delC; c.

View Article and Find Full Text PDF

Total hip arthroplasty with monobloc press-fit acetabular components and large-diameter bearings for atypical acetabula is safe: a consecutive case series of 125 hips with mean follow-up of 9 years.

Can J Surg

February 2024

From the Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, Que. (Synnott, Kiss, Shahin, Morcos, Binette, Vendittoli); the Department of Surgery, Université de Montréal, Montréal, Que. (Kiss, Morcos, Binette, Vendittoli); Clinique orthopédique Duval, Laval, Que. (Kiss, Vendittoli); and the Personalized Arthroplasty Society, Atlanta, Georgia (Vendittoli)

Article Synopsis
View Article and Find Full Text PDF

Carbonic Anhydrase II Deficiency: Unusual Presentation of the Arabic Mutation. A Case Report.

Glob Pediatr Health

February 2024

Department of Pediatrics, King Saud Medical City, Riyadh, Saudi Arabia.

Carbonic anhydrase II deficiency is an extremely rare inborn error of metabolism that constitutes a triad osteopetrosis, renal tubular acidosis and intracerebral calcification. Unlike other subtypes of osteopetrosis, the presence of developmental delay and relative infrequency of skeletal fractures may not be a typical signs of symptoms indolent trajectory. This case report demonstrates a 11-year-old boy who had a bilateral midshaft tibial fracture despite low mechanism of injury.

View Article and Find Full Text PDF

Autosomal Dominant Osteopetrosis type II (ADO2) is a rare bone disease of impaired osteoclastic bone resorption that usually results from heterozygous missense mutations in the chloride channel 7 (CLCN7) gene. We previously created mouse models of ADO2 (p.G213R) with one of the most common mutations (G215R) as found in humans and demonstrated that this mutation in mice phenocopies the human disease of ADO2.

View Article and Find Full Text PDF

Microglia, professional phagocytic cells of the brain, rely upon the appropriate activation of lysosomes to execute their immune and clearance functions. Lysosomal activity is, in turn, modulated by a complex network of over 200 membrane and accessory proteins that relay extracellular cues to these key degradation centers. The ClC-7 chloride (Cl-)-proton (H+) antiporter (also known as CLCN7) is localized to the endolysosomal compartments and mutations in CLCN7 lead to osteopetrosis and neurodegeneration.

View Article and Find Full Text PDF

Osteopetrosis is a heterogenous group of inheritable disorders which manifests as increased bone density and brittleness. The most common and mildest variant typically presents in adulthood with bone pain and pathologic fractures, including spondylolysis. We present the case of an otherwise healthy, active 17-year-old male with a history of osteopetrosis and 1 year of chronic back pain, found to have multilevel (L1-L4) spondylolysis in the setting of severe diffuse bony sclerosis consistent with osteopetrosis.

View Article and Find Full Text PDF

Context: Autosomal dominant osteopetrosis (ADO) is a rare genetic disorder resulting from impaired osteoclastic bone resorption. Clinical manifestations frequently include fractures, osteonecrosis (particularly of the jaw or maxilla), osteomyelitis, blindness, and/or bone marrow failure. ADO usually results from heterozygous missense variants in the Chloride Channel 7 gene (CLCN7) that cause disease by a dominant negative mechanism.

View Article and Find Full Text PDF

Osteoclast Methods in Protein Phosphatase Research.

Methods Mol Biol

December 2023

Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.

Osteoclasts are specialized cells that degrade bone and are essential for bone formation and maintaining bone homeostasis. Excess or deficient activity of these cells can significantly alter bone mass, structure, and physical strength, leading to significant morbidity, as in osteoporosis or osteopetrosis, among many other diseases. Protein phosphorylation in osteoclasts plays critical roles in the signaling pathways that govern the production of osteoclasts and regulate their bone-resorbing activity.

View Article and Find Full Text PDF

ClC-7 is a ubiquitously expressed voltage-gated Cl/H exchanger that critically contributes to lysosomal ion homeostasis. Together with its β-subunit Ostm1, ClC-7 localizes to lysosomes and to the ruffled border of osteoclasts, where it supports the acidification of the resorption lacuna. Loss of ClC-7 or Ostm1 leads to osteopetrosis accompanied by accumulation of storage material in lysosomes and neurodegeneration.

View Article and Find Full Text PDF

Background: Osteopetrosis comprises a group of inherited disorders that are rare and result in abnormal bone structure. Bone remodeling is extremely inhibited because osteoclasts are nonfunctional or lacking. This condition causes overgrowth of bone with disappearance of the bone marrow, leading to aplastic anemia; obstruction of nerve passages in the skull leads to blindness and often hearing impairment.

View Article and Find Full Text PDF

Centrosome clustering control in osteoclasts through CCR5-mediated signaling.

Sci Rep

November 2023

Department of Pharmacology, Faculty and Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586, Japan.

Osteoclasts uniquely resorb calcified bone matrices. To exert their function, mature osteoclasts maintain the cellular polarity and directional vesicle trafficking to and from the resorbing bone surface. However, the regulatory mechanisms and pathophysiological relevance of these processes remain largely unexplored.

View Article and Find Full Text PDF

Surgical outcome of distal tibia Salter Harris II fracture in osteopetrosis patient.

Int J Surg Case Rep

December 2023

Department of Orthopaedics & Traumatology, Ciptomangunkusumo General Hospital and Faculty of Medicine, Universitas Indonesia, Jalan Diponegoro No. 71, Salemba Jakarta Pusat, Jakarta 10430, Indonesia.

Introduction: Osteopetrosis is a rare genetic disorder characterized by increased bone density. This condition is clinically manifested with a brittle intramedullary structure and reduced bone toughness, increasing the risk of fracture. A limited case has been reported on the management of physeal fracture in patients with osteopetrosis.

View Article and Find Full Text PDF

Sensitivity Analysis of Upper Limb Musculoskeletal Models During Isometric and Isokinetic Tasks.

J Biomech Eng

February 2024

J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Drive, BMS JG-56, P. O. Box 116131 Gainesville, FL 32611.

Sensitivity coefficients are used to understand how errors in subject-specific musculoskeletal model parameters influence model predictions. Previous sensitivity studies in the lower limb calculated sensitivity using perturbations that do not fully represent the diversity of the population. Hence, the present study performs sensitivity analysis in the upper limb using a large synthetic dataset to capture greater physiological diversity.

View Article and Find Full Text PDF

() is a Gram-positive coccus of the family . It can be found in a variety of vegetables and dairy products. is an opportunistic pathogen with intrinsic resistance to vancomycin and teicoplanin.

View Article and Find Full Text PDF

Background: Osteopetrosis is a rare disease characterized by systemic osteosclerosis and hematopoietic disturbances. Childhood-onset cases are often accompanied by hydrocephalus and craniosynostosis; however, there have been no established treatments. We performed cranial distraction in a child with osteopetrosis who presented with craniosynostosis and intracranial hypertension.

View Article and Find Full Text PDF
Article Synopsis
  • - ClC-6 and ClC-7 are intracellular proteins that help regulate chloride (Cl) and hydrogen ions (H) in late endosomes and lysosomes, but they function differently, with ClC-7 needing another protein called Ostm1 to operate properly.
  • - Experiments showed that lower levels of external Cl reduce ClC-6 function, while they enhance ClC-7's activity, particularly under acidic conditions or low internal Cl levels.
  • - The study highlighted unique functions and responses of both transporters, indicating that ClC-7's ability to handle Cl may contribute to disease processes like osteopetrosis, emphasizing the need for balanced ion levels in cellular environments.
View Article and Find Full Text PDF

Background: Osteosclerotic metaphyseal dysplasia (OSMD, OMIM 615198) is an extremely rare autosomal recessive osteopetrosis disorder resulting in a distinctive pattern of osteosclerosis of the metaphyseal margins of long tubular bones. To date, only thirteen cases have been reported (eight molecularly confirmed). Five homozygous sequence variants in the leucine-rich repeat kinase 1 () gene have been identified to cause OSMD.

View Article and Find Full Text PDF

Osteopetrosis encompasses a spectrum of conditions marked by heightened bone density due to faulty osteoclast-mediated bone resorption, leading to an accumulation of immature bone and thickened cortical structures. This condition gives rise to bone fragility, blood cell irregularities, nerve entrapment and growth challenges, all stemming from disrupted bone remodelling. Craniofacial distinctiveness, encompassing anomalies in the skull and jaw, is a frequent occurrence.

View Article and Find Full Text PDF

[Analysis of clinical presentation and genetic characteristics of malignant infantile osteopetrosis].

Zhonghua Er Ke Za Zhi

November 2023

Hematology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing 100045, China.

To investigate the clinical presentation and genetic characteristics of malignant infantile osteopetrosis. This was a retrospective case study. Thirty-seven children with malignant infantile osteopetrosis admitted into Beijing Children's Hospital from January 2013 to September 2022 were enrolled in this study.

View Article and Find Full Text PDF