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European Journal of Medical Genetics Jul 2019Ophthalmo-acromelic syndrome is a rare autosomal recessive disorder characterized by ocular and skeletal abnormalities. Ocular findings present as a wide spectrum,... (Review)
Review
Ophthalmo-acromelic syndrome is a rare autosomal recessive disorder characterized by ocular and skeletal abnormalities. Ocular findings present as a wide spectrum, ranging from mild microphthalmia to true anophthalmia. Short 5th finger, synostosis of 4th and 5th metacarpals, and oligodactyly in feet are frequent limb malformations. Homozygous variants in the SMOC1 gene (SPARC-related modular calcium-binding protein 1 gene) were identified as causative for the syndrome. A 9-month-old female patient is presented herein, who was diagnosed with ophthalmo-acromelic syndrome and had a homozygous nonsense mutation (p.Arg75Ter) in SMOC1, along with a review of the literature.
Topics: Codon, Nonsense; Female; Homozygote; Humans; Infant; Osteonectin; Waardenburg Syndrome
PubMed: 31067494
DOI: 10.1016/j.ejmg.2019.05.003 -
Advances in Protein Chemistry and... 2023The human osteosarcoma is a malignant tumor of the arthro-skeletal system. It has been recognized that it is the most common malignancy followed by the Ewing sarcoma or... (Review)
Review
The human osteosarcoma is a malignant tumor of the arthro-skeletal system. It has been recognized that it is the most common malignancy followed by the Ewing sarcoma or primitive neuroectodermal tumor. The prognosis is worrisome and is not preserved by the use of classical chemotherapy drugs. High rates of recurrence and metastases often accompany this malignant tumor. Chemotherapy often fails because of the onset of multidrug resistance, even though the mechanism to reach chemotherapy resistance is still intriguing and contains unclear pathways. The secreted protein acidic and rich in cysteine (SPARC) or osteonectin (ON) (SPARC/ON) has been associated with poor prognosis in several malignant neoplasms. In this mini-review, we are going to highlight the role of SPARC/ON in human osteosarcoma. Extracellular vesicles are fundamental in cell-to-cell communication. We suggest that a liquid biopsy targeting SPARC/ON may be critical to implement in the surveillance of patients with this malignant bony neoplasm.
Topics: Humans; Osteonectin; Osteosarcoma; Bone Neoplasms
PubMed: 36707201
DOI: 10.1016/bs.apcsb.2022.10.007 -
Science Immunology Sep 2022Adipocyte derived SPARC induces pro-inflammatory changes to macrophages, leading to aging that can be reduced by caloric restriction.
Adipocyte derived SPARC induces pro-inflammatory changes to macrophages, leading to aging that can be reduced by caloric restriction.
Topics: Adipocytes; Humans; Inflammation; Macrophages; Osteonectin
PubMed: 36054338
DOI: 10.1126/sciimmunol.ade5698 -
Journal of Cellular Biochemistry Feb 2006The focus of this study was to gain insight into the role(s) of osteonectin in the preferential metastasis of breast cancer cells to bone. Osteonectin was isolated from...
The focus of this study was to gain insight into the role(s) of osteonectin in the preferential metastasis of breast cancer cells to bone. Osteonectin was isolated from conditioned media of several cell lines including breast cancer (MDA-MB-435, MDA-MB-468), osteoblasts (hFOB1.19), non-neoplastic breast epithelial (hTERT-HME1), and vascular endothelial cells isolated from a bone biopsy (HBME-1). Chemical/physical properties of osteonectin from these five sources was analyzed to determine if unique configurations of osteonectin exist and therefore identify a chemotactic isoform. Osteonectin from all sources had a molecular weight of approximately 46 kDa, N-linked glycosylation, and undetectable phosphorylated serines, sialic acids and O-linked oligosaccharides. The cDNA for osteonectin from the breast cancer, osteoblast, and breast epithelial cell lines was identical, while the vascular endothelial cell cDNA contained point mutations that resulted in eight amino acid substitutions. Bone-derived osteonectin was then analyzed to assess its influence on breast cancer cell motility and migration. Although osteonectin increased undirected MDA-MB-231 cell motility, it did not chemoattract the same breast cancer cell line. However, the breast cancer cells did migrate toward the known chemoattractant vitronectin and to bone extracts derived from wild-type and osteonectin-null mice. Migration to vitronectin was enhanced when osteonectin was also present. We concluded that osteonectin was not a chemotactic factor. However, through its anti-adhesive properties, osteonectin induced undirected breast cancer cell motility, and may have enhanced chemoattraction to vitronectin.
Topics: Amino Acid Sequence; Animals; Breast Neoplasms; Cell Line; Cell Line, Tumor; Cell Movement; Chemotaxis; DNA, Complementary; Glycosylation; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Sequence Data; Osteonectin; Phosphorylation; Vitronectin
PubMed: 16173048
DOI: 10.1002/jcb.20644 -
Bone 1992SPARC/Osteonectin is a major bone-related protein that is also present in nonmineralized tissues and in platelets. As compared to bone SPARC/Osteonectin,...
SPARC/Osteonectin is a major bone-related protein that is also present in nonmineralized tissues and in platelets. As compared to bone SPARC/Osteonectin, SPARC/Osteonectin from platelets presents a slightly lower electrophoretic mobility in SDS-PAGE and a 100-fold decreased affinity for a unique monoclonal antibody, Mab2 (Malaval et al. 1991). To check the tissular diversity of SPARC/Osteonectin, protein extracts from bovine bone, nonmineralized tissues, and platelets were screened by immunoblotting and immunoradiometric assay, with Mab2 and three other monoclonal antibodies recognizing distinct epitopes. The SPARC/Osteonectin secreted by a human osteosarcoma cell line (MG63) was also tested. In all the nonmineralized tissues tested (gut, bone marrow, tendon, mesentery, artera, lens, skin, liver, and cornea), SPARC/Osteonectin presents the same immunoreactivity and electrophoretic mobility as in bone. The heavier molecular weight and Mab2-negative form present in platelets seems to be unique to this cell type. Osteosarcoma cell extracts and conditioned media give the same results as bone extracts, indicating that the low molecular weight and Mab2-positive form of SPARC/Osteonectin present in most tissues does not result from proteolytic cleavage in the matrix, but is secreted as such. Bone and platelet SPARC/Osteonectin present different patterns of sensitivity to glycosidases, suggestive of a difference in N-glycosylation. However, these treatments do not affect the decreased affinity of Mab2 for platelet SPARC/Osteonectin, which is not likely to be related to difference in N-glycosylation.
Topics: Animals; Antibodies, Monoclonal; Autoradiography; Blood Platelets; Bone and Bones; Cattle; Chromatography, Ion Exchange; Electrophoresis, Polyacrylamide Gel; Fetus; Glycosylation; Humans; Hydroxyapatites; Immunoblotting; Immunoradiometric Assay; Molecular Weight; Organ Specificity; Osteonectin; Osteosarcoma; Radioimmunoassay; Tumor Cells, Cultured
PubMed: 1637573
DOI: 10.1016/8756-3282(92)90206-c -
Molecular Biology Reports Oct 2018Canine primary bone tumors have a plastic radiographic image, demanding histopathological confirmation. Bone tumors are characterized by the type and amount of...
Canine primary bone tumors have a plastic radiographic image, demanding histopathological confirmation. Bone tumors are characterized by the type and amount of extracellular matrix produced what cannot be easily recognized, especially in biopsy samples. Identifying cellular markers that could aid diagnosis has supported various studies in oncological pathology. This study aimed to evaluate 22 canine primary bone neoplasms, establishing their histopathological diagnosis and evaluated vimentin, osteonectin and osteocalcin expression and their implication in diagnosis and prognosis. There were 12 productive osteoblastic osteosarcomas, six minimally productive osteoblastic osteosarcoma, two chondrosarcomas, one fibrosarcoma and one hemangiosarcoma. Immunostaining was cytoplasmatic in all cases, with average percentage of 87.9% for vimentin, 98.0% for osteonectin and 99.9% for osteocalcin. In this last case, only osteosarcomas were considered. Intensity was higher in vimentin labeling (+++), followed by osteonectin (++) and osteocalcin (+). One osteosarcoma showed negative immunostaining for vimentin and of samples submitted to anti-osteocalcin immunostaining, three osteosarcomas and one fibrosarcoma had negative staining. Besides identifying mesenchymal origin, vimentin elevated expression in canine bone tumors can be related to epithelial-mesenchymal transition, leading to more aggressive tumoral phenotypes and metastasis development. Similarly, high osteonectin expression is implicated in neoplastic cell invasion and is also related to metastasis spread. Decreased osteocalcin expression was found in some osteosarcoma samples and can be related to poor prognosis, as in human osteosarcomas. Our findings suggest that vimentin, osteonectin and osteocalcin not only aid diagnosis but can be related to prognosis in canine primary bone tumors, especially osteosarcomas and its osteoblastic subtype.
Topics: Animals; Biomarkers, Tumor; Bone Neoplasms; Diagnosis, Differential; Dog Diseases; Dogs; Immunohistochemistry; Osteocalcin; Osteonectin; Osteosarcoma; Prognosis; Transcriptome; Vimentin
PubMed: 30066297
DOI: 10.1007/s11033-018-4285-6 -
Annals of Oncology : Official Journal... Apr 1992Seventy-five osteosarcomas at various grades of histologic differentiation were investigated for evidence of osteonectin. According to the results of the study,...
Seventy-five osteosarcomas at various grades of histologic differentiation were investigated for evidence of osteonectin. According to the results of the study, osteonectin was present in all osteosarcomas. An association between the intensity of the osteonectin antibody reaction and prognosis could not be established. Evidence of osteonectin was also found in other bone tumors. Osteonectin is therefore unsuitable for differential diagnosis, cannot be regarded as a bone specific protein and has not prognostic value.
Topics: Biomarkers, Tumor; Bone Neoplasms; Diagnosis, Differential; Humans; Immunohistochemistry; Osteonectin; Osteosarcoma; Prognosis
PubMed: 1622861
DOI: 10.1093/annonc/3.suppl_2.s33 -
The Journal of Clinical Investigation Apr 2000Bone continuously remodels in response to mechanical and physiological stresses, allowing vertebrates to renew bone as adults. Bone remodeling consists of the cycled...
Bone continuously remodels in response to mechanical and physiological stresses, allowing vertebrates to renew bone as adults. Bone remodeling consists of the cycled synthesis and resorption of collagenous and noncollagenous extracellular matrix proteins, and an imbalance in this process can lead to disease states such as osteoporosis, or more rarely, osteopetrosis. There is evidence that the extracellular matrix glycoprotein osteonectin or secreted protein acidic and rich in cysteine (BM-40) may be important in bone remodeling. Osteonectin is abundant in bone and is expressed in areas of active remodeling outside the skeleton. In vitro studies indicate that osteonectin can bind collagen and regulate angiogenesis, metalloproteinase expression, cell proliferation, and cell-matrix interactions. In some osteopenic states, such as osteogenesis imperfecta and selected animal models for bone fragility, osteonectin expression is decreased. To determine the function of osteonectin in bone, we used contact x-ray, histomorphometry, and Northern blot analysis to characterize the skeletal phenotype of osteonectin-null mice. We found that osteonectin-null mice have decreased bone formation and decreased osteoblast and osteoclast surface and number, leading to decreased bone remodeling with a negative bone balance and causing profound osteopenia. These data indicate that osteonectin supports bone remodeling and the maintenance of bone mass in vertebrates.
Topics: Animals; Bone Diseases, Metabolic; Bone Remodeling; Cell Count; Collagenases; Endothelial Growth Factors; Female; Lymphokines; Male; Matrix Metalloproteinase 13; Matrix Metalloproteinase 2; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoblasts; Osteocalcin; Osteoclasts; Osteonectin; Radiography; Spine; Tibia; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 10749571
DOI: 10.1172/JCI7039 -
Journal of Bone and Mineral Research :... Apr 2005The skeleton is the main source of osteonectin mRNA in adults of the seawater teleost sea bream Sparus auratus. It is expressed by cells forming the basement membrane of...
UNLABELLED
The skeleton is the main source of osteonectin mRNA in adults of the seawater teleost sea bream Sparus auratus. It is expressed by cells forming the basement membrane of calcifying tissue indicating that, as in mammals, it may play a role in osteoblast differentiation. PTHrP induced downregulation of osteonectin mRNA in vitro in scales, a mineralizing tissue with bone-like metabolism. This indicates a means to redirect calcium to activities such as vitellogenesis when this ion is in high demand.
INTRODUCTION
Osteonectin is a unique matricellular calcium-binding glycoprotein and a major noncollagenous constituent of higher eukaryote bone. In terrestrial vertebrates, it has been associated with development, remodeling, cell turnover, and tissue repair, all processes involving substantial changes in extracellular matrix (ECM) structure. In skeleton biology, osteonectin has been described as a positive factor in the mineralization process as well as in osteoblastic cell lineage differentiation and is downregulated by the hypercalcemic hormone PTH. In this study, we report the cloning and characterization of bream S. auratus osteonectin cDNA and its tissue and cellular distribution. Its high expression by fish scales provides a unique in vitro bioassay with which to study regulation of osteonectin gene expression by the recently isolated piscine PTH-related peptide (PTHrP).
MATERIALS AND METHODS
An intervertebral tissue cDNA library from S. auratus was the source of the full-length cDNA clone for osteonectin. Expression studies were performed by semiquantitative RT-PCR, Northern blot, and in situ hybridization analysis. Moreover, an in vitro bioassay with S. auratus scales was specifically developed for measuring the effect of PTHrP on osteonectin expression.
RESULTS AND CONCLUSIONS
Phylogenetic analysis showed that S. auratus osteonectin is highly homologous with previously reported osteonectins, supporting the idea of a conserved function for this protein in the ECM. Its expression pattern in adult tissues from S. auratus was markedly biased toward skeletal structures of both dermal or endochondral origin. More specifically, the localization of the osteonectin mRNA in the basement membrane that separates the epithelia from the underlying mineralized connective tissue supports a role for this protein in calcified matrix turnover. Furthermore, the recently identified piscine hypercalcemic factor PTHrP downregulates osteonectin expression in scales, suggesting a catabolic action for this hormone on these structures.
Topics: Amino Acid Sequence; Animals; Base Sequence; DNA, Complementary; Down-Regulation; Gene Expression; Molecular Sequence Data; Osteonectin; Parathyroid Hormone-Related Protein; Phylogeny; RNA, Messenger; Sea Bream; Sequence Alignment; Tissue Distribution; Vitellogenesis
PubMed: 15765188
DOI: 10.1359/JBMR.041201 -
Immunity Sep 2022Caloric restriction (CR) reduces inflammation and the incidence of chronic diseases, thereby extending healthspan and lifespan. In this issue of Immunity, Ryu et al....
Caloric restriction (CR) reduces inflammation and the incidence of chronic diseases, thereby extending healthspan and lifespan. In this issue of Immunity, Ryu et al. (2022) propose that reduction of SPARC, a matricellular protein, during CR offers beneficial effects by reducing SPARC-driven inflammatory phenotypes in macrophages.
Topics: Caloric Restriction; Humans; Inflammation; Longevity; Osteonectin
PubMed: 36103855
DOI: 10.1016/j.immuni.2022.08.012