Role of anoctamin 5, a gene associated with gnathodiaphyseal dysplasia, in osteoblast and osteoclast differentiation

Kim, Jung Ha; Kim, Kabsun; Kim, In-Young; Seong, Semun; Kim, Sang Wan; Kim, Nacksung

doi:10.1016/j.bone.2018.12.010

Cited by 11 publications

(17 citation statements)

References 44 publications

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“…Gnathodiaphyseal dysplasia is associated with mutations in ANO5 ( 71), a gene not known to be involved in collagen production or processing; and the overlap in phenotype between these conditions is not fully understood. However, recent studies have suggested that ANO5 may be involved in osteoclast regulation (104).…”

Section: Localized Increases In Bmdmentioning

confidence: 99%

The Genetic Architecture of High Bone Mass

Gregson

Duncan

2020

Front. Endocrinol.

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The phenotypic trait of high bone mass (HBM) is an excellent example of the nexus between common and rare disease genetics. HBM may arise from carriage of many 'high bone mineral density [BMD]'-associated alleles, and certainly the genetic architecture of individuals with HBM is enriched with high BMD variants identified through genome-wide association studies of BMD. HBM may also arise as a monogenic skeletal disorder, due to abnormalities in bone formation, bone resorption, and/or bone turnover. Individuals with monogenic disorders of HBM usually, though not invariably, have other skeletal abnormalities (such as mandible enlargement) and thus are best regarded as having a skeletal dysplasia rather than just isolated high BMD. A binary etiological division of HBM into polygenic vs. monogenic, however, would be excessively simplistic: the phenotype of individuals carrying rare variants of large effect can still be modified by their common variant polygenic background, and by the environment. HBM disorders-whether predominantly polygenic or monogenic in origin-are not only interesting clinically and genetically: they provide insights into bone processes that can be exploited therapeutically, with benefits both for individuals with these rare bone disorders and importantly for the many people affected by the commonest bone disease worldwidei.e., osteoporosis. In this review we detail the genetic architecture of HBM; we provide a conceptual framework for considering HBM in the clinical context; and we discuss monogenic and polygenic causes of HBM with particular emphasis on anabolic causes of HBM.

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Section: Localized Increases In Bmdmentioning

confidence: 99%

The Genetic Architecture of High Bone Mass

Gregson

Duncan

2020

Front. Endocrinol.

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“…According to the different expressions of marker genes, Cluster 2 was identified as mesenchymal stem cell (MSC), which was associated with a high expression of ITGB1, VACAM1, THY‐1 (CD90), NT5E (CD73), and ENG (CD105) 11 , 12 , 13 and negatively associated with hematopoietic stem cell gene markers such as CD34 and PTPRC. Cluster 5 was associated with high expression of osteoblast markers such as RUNX2, COLA1, SPP1, and ANO5, 14 , 15 , 16 which was annotated as osteoblast (OB). Cluster 3 was annotated as chondrocyte progenitor cell (CPC) for the high expression of BIRC5, UBE2C, and DHFR.…”

Section: Resultsmentioning

confidence: 99%

“…mito, percentage of mitochondrial genes expressions of marker genes, Cluster 2 was identified as mesenchymal stem cell (MSC), which was associated with a high expression of ITGB1, VACAM1, THY-1 (CD90), NT5E (CD73), and ENG (CD105) [11][12][13] and negatively associated with hematopoietic stem cell gene markers such as CD34 and PTPRC. Cluster 5 was associated with high expression of osteoblast markers such as RUNX2, COLA1, SPP1, and ANO5, [14][15][16] F I G U R E 2 ScRNA-seq analysis of immune-related cell group. A, t-SNE plots of subclusters of immunocytes.…”

Section: Scrna-seq Identified Multiple Cell Types In Control Subjects and Ais Patientsmentioning

confidence: 99%

Single‐cell RNA Seq reveals cellular landscape‐specific characteristics and potential etiologies for adolescent idiopathic scoliosis

Yang

Shi

et al. 2021

JOR Spine

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Backgrounds: Abnormal vertebral growth and development have been found in adolescent idiopathic scoliosis (AIS) patients, and the proliferation and differentiation of bone development-related cells play important roles in its pathogenesis. However, a comprehensive single-cell-level differentiation roadmap in AIS has not been achieved. Methods:The present study compared the single-cell level cellular landscapes of spinal cancellous bone tissues between AIS patients and healthy subjects using high throughput single-cell RNA sequencing (scRNA-seq), which covers multiple cellular lineages including osteoblast, chondrocyte, osteoclast and related immunocytes. We constructed the differentiation trajectories of bone development-related cell lineages through pseudotime analysis, and the intercellular-communication networks between bone development-related cells and immunocytes were further developed.Results: A total of 11 distinct cell clusters were identified according to the genome-wide transcriptome profiles. t-Distributed stochastic neighbor embedding (t-SNE) analysis showed that mesenchymal stem cells (MSC) were classified into three subtypes: MSC-LOXL2, MSC-IGFBP5, and MSC-GJA1. Gene ontology (GO) analysis showed that MSC-GJA1 might possess greater osteoblast differentiation potential than the others. MSC-IGFBP5 was the specific MSC subtype observed only in AIS. There were two distinct gene expression clusters: OB-DPT and OB-OLFML2B, and the counts of osteoblasts derived from AIS was significantly less than that of non-AIS subjects. In AIS patients, MSC-IGFBP5 failed to differentiate into osteoblasts and exhibited negative regulation of cell proliferation and enhanced cell death. CPC-PCNA was found to be the specific chondrocyte progenitor cell (CPC) subtype observed only in AIS patients. The cell counts of OC-BIRC3 in AIS were less than those in controls. Pseudotime analysis suggested two possible distinct osteoclast differentiation patterns in AIS and control subjects. Monocytes in AIS mainly differentiated into OC-CRISP3.

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“…Structural studies of TMEM16E will be needed to clarify the precise mechanism by which phosphatidylserine is exposed on the cell surface of myoblasts. Furthermore, TMEM16E regulates osteoclast differentiation [98], and its gain-of-function mutation leads to gnathodiaphyseal dysplasia (GDD) with abnormal bone remodeling [99]. However, whether phospholipid scrambling activity of TMEM16E is involved in osteoclast fusion remains to be clarified.…”

Section: Myoblast Fusionmentioning

confidence: 99%

Stabilin Receptors: Role as Phosphatidylserine Receptors

Park

Kim

2019

Biomolecules

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Phosphatidylserine is a membrane phospholipid that is localized to the inner leaflet of the plasma membrane. Phosphatidylserine externalization to the outer leaflet of the plasma membrane is an important signal for various physiological processes, including apoptosis, platelet activation, cell fusion, lymphocyte activation, and regenerative axonal fusion. Stabilin-1 and stabilin-2 are membrane receptors that recognize phosphatidylserine on the cell surface. Here, we discuss the functions of Stabilin-1 and stabilin-2 as phosphatidylserine receptors in apoptotic cell clearance (efferocytosis) and cell fusion, and their ligand-recognition and signaling pathways.

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Role of anoctamin 5, a gene associated with gnathodiaphyseal dysplasia, in osteoblast and osteoclast differentiation

Cited by 11 publications

References 44 publications

The Genetic Architecture of High Bone Mass

The Genetic Architecture of High Bone Mass

Single‐cell RNA Seq reveals cellular landscape‐specific characteristics and potential etiologies for adolescent idiopathic scoliosis

Stabilin Receptors: Role as Phosphatidylserine Receptors

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