scholarly journals Selective enrichment of microRNAs in extracellular matrix vesicles produced by growth plate chondrocytes

Bone ◽  
2016 ◽  
Vol 88 ◽  
pp. 47-55 ◽  
Author(s):  
Zhao Lin ◽  
Nicholas E. Rodriguez ◽  
Junjun Zhao ◽  
Allison N. Ramey ◽  
Sharon L. Hyzy ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Plate ◽  
Matrix Vesicles ◽  
Growth Plate Chondrocytes ◽  
Selective Enrichment

scholarly journals MicroRNA Contents in Matrix Vesicles Produced by Growth Plate Chondrocytes are Cell Maturation Dependent

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Zhao Lin ◽  
Michael J. McClure ◽  
Junjun Zhao ◽  
Allison N. Ramey ◽  
Niels Asmussen ◽  
...  
Keyword(s):  
Growth Plate ◽  
Matrix Vesicles ◽  
Cell Maturation ◽  
Growth Plate Chondrocytes

scholarly journals Retinoic acid stimulates annexin-mediated growth plate chondrocyte mineralization

2002 ◽  
Vol 157 (6) ◽  
pp. 1061-1070 ◽  
Author(s):  
Wei Wang ◽  
Thorsten Kirsch
Keyword(s):  
Gene Expression ◽  
Alkaline Phosphatase ◽  
Retinoic Acid ◽  
Growth Plate ◽  
Calcium Concentration ◽  
Matrix Vesicles ◽  
Cytosolic Calcium ◽  
Annexin Ii ◽  
Growth Plate Chondrocytes ◽  
Cytosolic Calcium Concentration

Biomineralization is a highly regulated process that plays a major role during the development of skeletal tissues. Despite its obvious importance, little is known about its regulation. Previously, it has been demonstrated that retinoic acid (RA) stimulates terminal differentiation and mineralization of growth plate chondrocytes (Iwamoto, M., I.M. Shapiro, K. Yagumi, A.L. Boskey, P.S. Leboy, S.L. Adams, and M. Pacifici. 1993. Exp. Cell Res. 207:413–420). In this study, we provide evidence that RA treatment of growth plate chondrocytes caused a series of events eventually leading to mineralization of these cultures: increase in cytosolic calcium concentration, followed by up-regulation of annexin II, V, and VI gene expression, and release of annexin II–, V–, VI– and alkaline phosphatase–containing matrix vesicles. Cotreatment of growth plate chondrocytes with RA and BAPTA-AM, a cell permeable Ca2+ chelator, inhibited the up-regulation of annexin gene expression and mineralization of these cultures. Interestingly, only matrix vesicles isolated from RA-treated cells that contained annexins, were able to take up Ca2+ and mineralize, whereas vesicles isolated from untreated or RA/BAPTA-treated cells, that contained no or only little annexins were not able to take up Ca2+ and mineralize. Cotreatment of chondrocytes with RA and EDTA revealed that increases in the cytosolic calcium concentration were due to influx of extracellular calcium. Interestingly, the novel 1,4-benzothiazepine derivative K-201, a specific annexin Ca2+ channel blocker, or antibodies specific for annexin II, V, or VI inhibited the increases in cytosolic calcium concentration in RA-treated chondrocytes. These findings indicate that annexins II, V, and VI form Ca2+ channels in the plasma membrane of terminally differentiated growth plate chondrocytes and mediate Ca2+ influx into these cells. The resulting increased cytosolic calcium concentration leads to a further up-regulation of annexin II, V, and VI gene expression, the release of annexin II–, V–, VI– and alkaline phosphatase–containing matrix vesicles, and the initiation of mineralization by these vesicles.

scholarly journals Growth Plate Genes Are Key Regulators of Growth: Lessons Learned From Children of Consanguineous Families From Kurdistan, Iraq

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A723-A724
Author(s):  
Shenali Anne Amaratunga ◽  
Tara Hussein Tayeb ◽  
Petra Dusatkova ◽  
Lenka Elblova ◽  
Stepanka Pruhova ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Short Stature ◽  
Growth Plate ◽  
Growth Regulation ◽  
Genetic Diagnosis ◽  
Human Growth ◽  
Lessons Learned ◽  
Growth Plate Chondrocytes ◽  
Pathogenic Variants ◽  
Families With Children

Abstract Introduction: The genetic basis of human growth regulation has only been partly elucidated thus far. Therefore, finding causative genes in patients with short stature help in understanding precise pathophysiological mechanisms, establishing genotype-phenotype relationships and optimizing treatment. In order to extend our knowledge about the genes involved in short stature, we studied a unique cohort of consanguineous families with children with short stature from Sulaymani in Kurdistan, Iraq. Patients and Methods: Fifty-five consanguineous families, with children shorter than -2.3SDS at the time of examination (median height -3.3SDS, range -2.3 to -15SDS), who were examined at the endocrine outpatient clinic of the Department of Pediatrics, Sulaymani University College of Medicine between January 2018 and February 2020, were included in the study. In families with more than one child with short stature, the shorter sibling was selected as the proband (median age 8 years, range 1 - 15 years). Three probands were subsequently excluded due to the diagnosis of Turner’s syndrome and Edward’s syndrome Consent was obtained from all families and probands’ DNA was analyzed by Whole Exome Sequencing (WES) methods. The data were processed by a bioinformatic pipeline and detected variants were filtered using variant analysis software. Selected potentially pathogenic variants were confirmed using Sanger sequencing methods and evaluated by the American College of Medical Genetics (ACMG) standards and guidelines. Results: A monogenic cause of short stature, which explained the patient phenotype, was elucidated in 13 of 26 families who were analyzed thus far. Seven families had multiple affected children making a total of 22 patients with a positive genetic diagnosis. Pathogenic or likely pathogenic variants (according to the ACMG standards) were found in genes involved in the GH-IGF-1 axis (GHR), in the extracellular matrix of the growth plate (COL1A2, MMP13, LTBP3, and ADAMTS17), in the regulation of chondrocytes (NPR2 and CTSK), transporter coding genes (SLC34A3), and other genes (PTCH1, GALNS, DNACJ21, ZSWIM6, GNPTG). Among them, there are 9 novel variants and 10 homozygous variants including variants in genes causing syndromic short stature. Unexpectedly, we successfully identified three cases of autosomal dominant short stature (variants in genes NPR2, COL1A2, PTCH1) as well. The remaining probands from 26 families are still being analyzed. Conclusion: With the help of NGS methods, we have successfully elucidated the genetic cause of short stature in nearly 50% of patients who were analyzed thus far. These results further strength the concept that genes affecting the growth plate (chondrocytes and the extracellular matrix) play a crucial role in growth regulation. Acknowledgements: The study was co-funded by grants AZV 18-07-00283 and GAUK 340420.

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