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International Journal of Molecular... May 2024Primary hip osteoarthritis (pOA) develops without an apparent underlying reason, whereas secondary osteoarthritis arises due to a known cause, such as developmental...
Distinctiveness of Femoral and Acetabular Mesenchymal Stem and Progenitor Populations in Patients with Primary and Secondary Hip Osteoarthritis Due to Developmental Dysplasia.
Primary hip osteoarthritis (pOA) develops without an apparent underlying reason, whereas secondary osteoarthritis arises due to a known cause, such as developmental dysplasia of the hips (DDH-OA). DDH-OA patients undergo total hip arthroplasty at a much younger age than pOA patients (50.58 vs. 65 years in this study). Recently, mesenchymal stem and progenitor cells (MSPCs) have been investigated for the treatment of osteoarthritis due to their immunomodulatory and regenerative potential. This study identified cells in subchondral bone expressing common MSPC markers (CD10, CD73, CD140b, CD146, CD164, CD271, GD2, PDPN) in vivo and compared the proportions of these populations in pOA vs. DDH-OA, further correlating them with clinical, demographic, and morphological characteristics. The differences in subchondral morphology and proportions of non-hematopoietic cells expressing MSPC markers were noted depending on OA type and skeletal location. Bone sclerosis was more prominent in the pOA acetabulum (Ac) in comparison to the DDH-OA Ac and in the pOA Ac compared to the pOA femoral head (Fh). Immunophenotyping indicated diagnosis-specific differences, such as a higher proportion of CD164+ cells and their subsets in DDH-OA, while pOA contained a significantly higher proportion of CD10+ and GD2+ cells and subsets, with CD271+ being marginally higher. Location-specific differences showed that CD271+ cells were more abundant in the Fh compared to the Ac in DDH-OA patients. Furthermore, immunohistochemical characterization of stromal bone-adjacent cells expressing MSPC markers (CD10, CD164, CD271, GD2) in the Ac and Fh compartments was performed. This research proved that immunophenotype profiles and morphological changes are both location- and disease-specific. Furthermore, it provided potentially effective targets for therapeutic strategies. Future research should analyze the differentiation potential of subsets identified in this study. After proper characterization, they can be selectively targeted, thus enhancing personalized medicine approaches in joint disease management.
Topics: Humans; Mesenchymal Stem Cells; Female; Male; Osteoarthritis, Hip; Middle Aged; Aged; Acetabulum; Developmental Dysplasia of the Hip; Adult; Biomarkers; Femur; Immunophenotyping
PubMed: 38791213
DOI: 10.3390/ijms25105173 -
Medicine May 2024Cartilage-hair hypoplasia (CHH, OMIM # 250250) is a rare autosomal recessive disorder, which includes cartilage-hair hypoplasia-anauxetic dysplasia (CHH-AD) spectrum...
RATIONALE
Cartilage-hair hypoplasia (CHH, OMIM # 250250) is a rare autosomal recessive disorder, which includes cartilage-hair hypoplasia-anauxetic dysplasia (CHH-AD) spectrum disorders. CHH-AD is caused by homozygous or compound heterozygous mutations in the RNA component of the mitochondrial RNA-processing Endoribonuclease (RMRP) gene.
PATIENT CONCERNS
Here, we report 2 cases of Korean children with CHH-AD.
DIAGNOSES
In the first case, the patient had metaphyseal dysplasia without hypotrichosis, diagnosed by whole exome sequencing (WES), and exhibited only skeletal dysplasia and lacked extraskeletal manifestations, such as hair hypoplasia and immunodeficiency. In the second case, the patient had skeletal dysplasia, hair hypoplasia, and immunodeficiency, which were identified by WES.
INTERVENTIONS
The second case is the first CHH reported in Korea. The patients in both cases received regular immune and lung function checkups.
OUTCOMES
Our cases suggest that children with extremely short stature from birth, with or without extraskeletal manifestations, should include CHH-AD as a differential diagnosis.
LESSONS SUBSECTIONS
Clinical suspicion is the most important and RMRP sequencing should be considered for the diagnosis of CHH-AD.
Topics: Humans; Republic of Korea; Osteochondrodysplasias; Male; Female; Hair; Hirschsprung Disease; Mutation; Dwarfism; Primary Immunodeficiency Diseases; Hypotrichosis; Exome Sequencing; Infant; Child, Preschool; Endoribonucleases; Child; RNA, Long Noncoding
PubMed: 38787970
DOI: 10.1097/MD.0000000000037247 -
BMC Oral Health May 2024Cleidocranial dysplasia (CCD) is an autosomal dominant hereditary disorder. Besides skeletal abnormalities, CCD is often associated with dental complications, such as...
BACKGROUND
Cleidocranial dysplasia (CCD) is an autosomal dominant hereditary disorder. Besides skeletal abnormalities, CCD is often associated with dental complications, such as multiple supernumerary teeth and permanent teeth impaction or delayed eruption.
METHODS
Supernumerary teeth of axial, sagittal and coronal CBCT view was characterized in detail and 3D image reconstruction was performed. Number and location of teeth, morphology of supernumerary teeth, positional relationship between supernumerary and adjacent permanent teeth, direction of supernumerary teeth in CCD patients were analyzed.
RESULTS
The mean age of the 3 CCD patients in this study was 16.7 years. Among 36 supernumerary teeth, the majority of them were identified as apical side located and lingual side located. Normal orientation was the most common type in this study, followed by sagittal orientation, and horizontal orientation. Horizontal orientation teeth were all distributed in the mandible. Supernumerary teeth exhibited significantly shorter crown and dental-root lengths, as well as smaller crown mesiodistal and buccolingual diameters (P < 0.01). There was no difference in the number of supernumerary teeth between the maxilla and mandible, and the premolars region had the largest number of supernumerary teeth and the incisor region had the smallest number.
CONCLUSIONS
This study compares number and location of teeth, morphology of supernumerary teeth, positional relationship between supernumerary and adjacent permanent teeth and direction of supernumerary teeth, this study also provides a reference for the comprehensive evaluation of CCD patients before surgery.
Topics: Humans; Cleidocranial Dysplasia; Tooth, Supernumerary; Imaging, Three-Dimensional; Cone-Beam Computed Tomography; Adolescent; Male; Female; Tooth Crown; Tooth Root; Odontometry; Young Adult; Mandible; Bicuspid; Maxilla; Image Processing, Computer-Assisted
PubMed: 38760743
DOI: 10.1186/s12903-024-04353-z -
Arthroplasty Today Jun 2024Dyggve-Melchior-Clausen (DMC) disease is a rare spondyloepiphyseal autosomal recessive disorder characterized by skeletal dysplasia and intellectual disability. Hip... (Review)
Review
Dyggve-Melchior-Clausen (DMC) disease is a rare spondyloepiphyseal autosomal recessive disorder characterized by skeletal dysplasia and intellectual disability. Hip arthritis, often secondary to hip dysplasia, presents at an early age. Current literature suggests that osteotomies do not benefit DMC syndrome-associated hip disease but reports of total hip arthroplasty in these patients are lacking. We present a case of bilateral hip replacement in a 31-year-old patient with DMC syndrome. After planning the operation with the use of computed tomography, we chose to use a small-dimension porous cup along with an appropriately sized version control stem in order to address the unique acetabular and femoral deformities. In conclusion, we consider total hip replacement in DMC syndrome to be safe and effective in addressing a challenging hip pathology.
PubMed: 38741921
DOI: 10.1016/j.artd.2024.101402 -
Heliyon May 2024Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia that presents with abnormalities in the craniofacial region, teeth, and clavicles and is...
INTRODUCTION
Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia that presents with abnormalities in the craniofacial region, teeth, and clavicles and is linked to mutation. Prenatal diagnoses of CCD have rarely been reported, and most of these cases have a positive family history. Here we report two prenatally diagnosed CCD cases without a positive family history. We conducted a literature review to summarize the prenatal sonographic findings of CCD.
CASE REPORTS
Case 1 (a 26-year-old woman): ultrasound at 13 weeks showed a thickened nuchal translucency with absent nasal bones and poor ossifications in the cranium and vertebrae. Genetic testing confirmed a frame shift deletion of . Case 2 (a 27-year-old woman): ultrasound at 32 weeks showed potential fetal skeletal dysplasia, with inadequate skull ossification, mild ossified bilateral clavicles, and frameshift deletion mutation. Both cases were diagnosed with CCD and the parents chose pregnancy termination.
CONCLUSION
These cases underscore the importance of sonographic examination for prenatal CCD diagnosis with a negative family history. By reviewing previous cases, we concluded that combining NB hypoplasia, clavicle and skull hypoplasia, and shortened long bones may be effective for early screening for CCD. Prenatal diagnosis is crucial for guiding medical decisions.
PubMed: 38737280
DOI: 10.1016/j.heliyon.2024.e29816 -
Journal of Clinical Medicine Apr 2024: Pycnodysostosis is a rare genetic disorder causing skeletal dysplasia. It is determined by a gene mutation leading to cathepsin K deficiency and predisposes a patient...
: Pycnodysostosis is a rare genetic disorder causing skeletal dysplasia. It is determined by a gene mutation leading to cathepsin K deficiency and predisposes a patient to osteosclerosis, resulting in increased bone fragility. The altered bone quality typical of this disease is responsible for an increased risk of fractures. The purpose of our study was to evaluate the orthopedic manifestations and potential pitfalls in the surgical treatments of pathological fractures in a series of patients treated in our institution who were affected by pycnodysostosis. : We retrospectively evaluated clinical and radiographic characteristics of five patients with pycnodysostosis treated for pathological fractures at our hospital in the past 5 years. : Two male and three female patients were included in this study. Four patients had a family history of pycnodysostosis. All the patients were of short stature, but only two underwent growth hormone treatment. All the patients experienced fractures, mostly in their lower limbs and occurring as a result of low-energy trauma. Most of the patients experienced either consolidation delay or nonunion. : The orthopedic management of fractures in patients with pycnodysostosis poses an ongoing challenge for orthopedic surgeons. The fact that the bone is simultaneously sclerotic and brittle makes any orthopedic surgical treatment challenging and at a high risk of nonunion in any case.
PubMed: 38731051
DOI: 10.3390/jcm13092522 -
Cellular Signalling Aug 2024Bone development involves the rapid proliferation and differentiation of osteogenic lineage cells, which makes accurate chromosomal segregation crucial for ensuring cell...
BACKGROUND
Bone development involves the rapid proliferation and differentiation of osteogenic lineage cells, which makes accurate chromosomal segregation crucial for ensuring cell proliferation and maintaining chromosomal stability. However, the mechanism underlying the maintenance of chromosome stability during the rapid proliferation and differentiation of Prx1-expressing limb bud mesenchymal cells into osteoblastic precursor cells remains unexplored.
METHODS
A transgenic mouse model of RanGAP1 knockout of limb and head mesenchymal progenitor cells was constructed to explore the impact of RanGAP1 deletion on bone development by histomorphology and immunostaining. Subsequently, G-banding karyotyping analysis and immunofluorescence staining were used to examine the effects of RanGAP1 deficiency on chromosome instability. Finally, the effects of RanGAP1 deficiency on chromothripsis and bone development signaling pathways were elucidated by whole-genome sequencing, RNA-sequencing, and qPCR.
RESULTS
The ablation of RanGAP1 in limb and head mesenchymal progenitor cells expressing Prx1 in mice resulted in embryonic lethality, severe cartilage and bone dysplasia, and complete loss of cranial vault formation. Moreover, RanGAP1 loss inhibited chondrogenic or osteogenic differentiation of mesenchymal stem cells (MSCs). Most importantly, we found that RanGAP1 loss in limb bud mesenchymal cells triggered missegregation of chromosomes, resulting in chromothripsis of chromosomes 1q and 14q, further inhibiting the expression of key genes involved in multiple bone development signaling pathways such as WNT, Hedgehog, TGF-β/BMP, and PI3K/AKT in the chromothripsis regions, ultimately disrupting skeletal development.
CONCLUSIONS
Our results establish RanGAP1 as a critical regulator of bone development, as it supports this process by preserving chromosome stability in Prx1-expressing limb bud mesenchymal cells.
Topics: Animals; Mice; Bone Development; Cell Differentiation; Chondrogenesis; Chromosomal Instability; Homeodomain Proteins; Limb Buds; Mesenchymal Stem Cells; Mice, Knockout; Osteogenesis; Signal Transduction
PubMed: 38729327
DOI: 10.1016/j.cellsig.2024.111222 -
Cells Apr 2024Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants of encoding for Gα and leading to excessive cyclic adenosine monophosphate...
Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants of encoding for Gα and leading to excessive cyclic adenosine monophosphate signaling in bone-marrow stromal cells (BMSCs). The effect of Gα activation in the BMSC transcriptome and how it influences FD lesion microenvironment are unclear. We analyzed changes induced by Gα activation in the BMSC transcriptome and secretome. RNAseq analysis of differential gene expression of cultured BMSCs from patients with FD and healthy volunteers, and from an inducible mouse model of FD, was performed, and the transcriptomic profiles of both models were combined to build a robust FD BMSC genetic signature. Pathways related to Gα activation, cytokine signaling, and extracellular matrix deposition were identified. To assess the modulation of several key secreted factors in FD pathogenesis, cytokines and other factors were measured in culture media. Cytokines were also screened in a collection of plasma samples from patients with FD, and positive correlations of several cytokines to their disease burden score, as well as to one another and bone turnover markers, were found. These data support the pro-inflammatory, pro-osteoclastic behavior of FD BMSCs and point to several cytokines and other secreted factors as possible therapeutic targets and/or circulating biomarkers for FD.
Topics: Humans; Animals; Mesenchymal Stem Cells; Transcriptome; Mice; Fibrous Dysplasia of Bone; Male; Female; Cytokines; GTP-Binding Protein alpha Subunits, Gs; Adult; Middle Aged
PubMed: 38727310
DOI: 10.3390/cells13090774 -
Cureus Apr 2024The assessment of sagittal skeletal dysplasia is crucial for accurate diagnosis and treatment planning, thus necessitating a thorough evaluation. A novel cephalometric...
INTRODUCTION
The assessment of sagittal skeletal dysplasia is crucial for accurate diagnosis and treatment planning, thus necessitating a thorough evaluation. A novel cephalometric parameter, known as the Zeta angle, was proposed in this study for the evaluation of the maxillomandibular relationship in the sagittal plane.
MATERIALS AND METHODS
This observational study was carried out using 291 pre-treatment lateral cephalograms of participants aged between 15 and 25 years, categorized into skeletal class I, II, and III relationships based on Wits appraisal, ANB angle, and Beta angle. The individuals reported to the Department of Orthodontics from January 2021 to October 2023, Manav Rachna Dental College, Manav Rachna International Institute of Research and Studies, Faridabad. The Zeta angle was constructed using three skeletal reference points as point Pt (pterygoid), point M (center of premaxilla), and point Pm (suprapogonion) and was measured perpendicular to point M on the Pt-Pm line and the M-Pm line to determine the severity and type of maxillomandibular discrepancy in the sagittal plane. Statistical tests were used to obtain the mean values for the Zeta angle. Analysis of variance (ANOVA), followed by the Bonferroni post-hoc test, was used to assess skeletal differences between the groups. Receiver operating characteristic (ROC) curves were used to evaluate the sensitivity and specificity of this angle.
RESULTS
The results indicated that a Zeta angle between 57° and 64° had a class I skeletal jaw pattern, a Zeta angle less than 57° indicated a class II skeletal jaw pattern, and a Zeta angle greater than 64° indicated a class III skeletal jaw pattern. ROC curves showed that a Zeta angle less than 57.5° had 80% sensitivity and 82.5% specificity in distinguishing class II from the class I subset. A Zeta angle greater than 64.5° has a sensitivity and specificity of 92.5% in distinguishing class III from the class I subset.
CONCLUSION
The Zeta angle may serve as an additional diagnostic tool for the reliable determination of sagittal jaw relationships due to its establishment based on stable anatomical points, thus remaining unaffected by jaw rotations and orthodontic treatments.
PubMed: 38721219
DOI: 10.7759/cureus.57788