Abstract
Endochondral bone formation is a precise and highly ordered process whose exact regulatory framework is still being elucidated. Multiple regulatory pathways are known to be involved. In some cases, regulation impacts gene expression, resulting in changes in chondrocyte phenotypic expression and extracellular matrix synthesis. Rapid regulatory mechanisms are also involved, resulting in release of enzymes, factors and micro RNAs stored in extracellular matrisomes called matrix vesicles. Vitamin D metabolites modulate endochondral development via both genomic and rapid membrane-associated signaling pathways. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] acts through the vitamin D receptor (VDR) and a membrane associated receptor, protein disulfide isomerase A3 (PDIA3). 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] affects primarily chondrocytes in the resting zone (RC) of the growth plate, whereas 1α,25(OH)2D3 affects cells in the prehypertrophic and upper hypertrophic cell zones (GC). This includes genomically directing the cells to produce matrix vesicles with zone specific characteristics. In addition, vitamin D metabolites produced by the cells interact directly with the matrix vesicle membrane via rapid signal transduction pathways, modulating their activity in the matrix. The matrix vesicle payload is able to rapidly impact the extracellular matrix via matrix processing enzymes as well as providing a feedback mechanism to the cells themselves via the contained micro RNAs.
| Original language | English (US) |
|---|---|
| Journal | Steroids |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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Keywords
- Chondrocyte cell membrane
- Exosomes
- Growth plate cartilage
- Matrisomes
- Matrix vesicles
- MiRNA
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Endocrinology
- Pharmacology
- Clinical Biochemistry
- Organic Chemistry
Cite this
Regulation of extracellular matrix vesicles via rapid responses to steroid hormones during endochondral bone formation. / Asmussen, Niels; Lin, Zhao; McClure, Michael J.; Schwartz, Zvi; Boyan, Barbara D.
In: Steroids, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of extracellular matrix vesicles via rapid responses to steroid hormones during endochondral bone formation
AU - Asmussen, Niels
AU - Lin, Zhao
AU - McClure, Michael J.
AU - Schwartz, Zvi
AU - Boyan, Barbara D.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Endochondral bone formation is a precise and highly ordered process whose exact regulatory framework is still being elucidated. Multiple regulatory pathways are known to be involved. In some cases, regulation impacts gene expression, resulting in changes in chondrocyte phenotypic expression and extracellular matrix synthesis. Rapid regulatory mechanisms are also involved, resulting in release of enzymes, factors and micro RNAs stored in extracellular matrisomes called matrix vesicles. Vitamin D metabolites modulate endochondral development via both genomic and rapid membrane-associated signaling pathways. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] acts through the vitamin D receptor (VDR) and a membrane associated receptor, protein disulfide isomerase A3 (PDIA3). 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] affects primarily chondrocytes in the resting zone (RC) of the growth plate, whereas 1α,25(OH)2D3 affects cells in the prehypertrophic and upper hypertrophic cell zones (GC). This includes genomically directing the cells to produce matrix vesicles with zone specific characteristics. In addition, vitamin D metabolites produced by the cells interact directly with the matrix vesicle membrane via rapid signal transduction pathways, modulating their activity in the matrix. The matrix vesicle payload is able to rapidly impact the extracellular matrix via matrix processing enzymes as well as providing a feedback mechanism to the cells themselves via the contained micro RNAs.
AB - Endochondral bone formation is a precise and highly ordered process whose exact regulatory framework is still being elucidated. Multiple regulatory pathways are known to be involved. In some cases, regulation impacts gene expression, resulting in changes in chondrocyte phenotypic expression and extracellular matrix synthesis. Rapid regulatory mechanisms are also involved, resulting in release of enzymes, factors and micro RNAs stored in extracellular matrisomes called matrix vesicles. Vitamin D metabolites modulate endochondral development via both genomic and rapid membrane-associated signaling pathways. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] acts through the vitamin D receptor (VDR) and a membrane associated receptor, protein disulfide isomerase A3 (PDIA3). 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] affects primarily chondrocytes in the resting zone (RC) of the growth plate, whereas 1α,25(OH)2D3 affects cells in the prehypertrophic and upper hypertrophic cell zones (GC). This includes genomically directing the cells to produce matrix vesicles with zone specific characteristics. In addition, vitamin D metabolites produced by the cells interact directly with the matrix vesicle membrane via rapid signal transduction pathways, modulating their activity in the matrix. The matrix vesicle payload is able to rapidly impact the extracellular matrix via matrix processing enzymes as well as providing a feedback mechanism to the cells themselves via the contained micro RNAs.
KW - Chondrocyte cell membrane
KW - Exosomes
KW - Growth plate cartilage
KW - Matrisomes
KW - Matrix vesicles
KW - MiRNA
UR - http://www.scopus.com/inward/record.url?scp=85039870775&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85039870775&partnerID=8YFLogxK
U2 - 10.1016/j.steroids.2017.12.003
DO - 10.1016/j.steroids.2017.12.003
M3 - Article
C2 - 29233620
AN - SCOPUS:85039870775
JO - Steroids
JF - Steroids
SN - 0039-128X
ER -