Abstract
We investigated stem cell factor (SCF) expression in osteoblasts because mast cells, which occur ectopically in hyperparathyroid bone, are induced by SCF. Nontransformed osteoblasts and Saos2 or MG63 cells expressed SCF in response to PTH. Western analysis showed only large, cell-associated isoforms, M(r)s ~ 40-48 kD. Transfection of MG63 cells with plasmids expressing antisense SCF mRNA eliminated immunoreactive SCF. Sequencing osteoblast SCF cDNAs showed that exon 6 was omitted. mRNAs without exon 6 produce membrane-associated SCF isoforms in rodents, suggesting that human SCFs are processed similarly. The major osteoblastic SCF mRNA, ~ 5 kB, was augmented by PTH. Neither protein or mRNA was increased by vitamin D, however, 6-7 kB transcripts were predominant in other tissues but not detectable in osteoblasts. We conclude that osteoblasts express SCF in response to PTH, with mRNA and protein processing differences relative to other cells. SCF stimulates osteoclasts, suggesting that PTH-induced osteoblastic SCF functions to accelerate bone turnover. Mast cells may occur due to SCF overexpression at extreme PTH levels.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 778-784 |
| Number of pages | 7 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 255 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 24 1999 |
| Externally published | Yes |
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Keywords
- 1,25-Dihydroxyvitamin D
- Bone turnover
- c-kit
- Mast cell
- Splice variant
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Parathyroid hormone-regulated production of stem cell factor in human osteoblasts and osteoblast-like cells. / Blair, Harry C.; Julian, Bruce A.; Cao, Xu; Jordan, S. Elizabeth; Dong, Sai Sai.
In: Biochemical and Biophysical Research Communications, Vol. 255, No. 3, 24.02.1999, p. 778-784.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Parathyroid hormone-regulated production of stem cell factor in human osteoblasts and osteoblast-like cells
AU - Blair, Harry C.
AU - Julian, Bruce A.
AU - Cao, Xu
AU - Jordan, S. Elizabeth
AU - Dong, Sai Sai
PY - 1999/2/24
Y1 - 1999/2/24
N2 - We investigated stem cell factor (SCF) expression in osteoblasts because mast cells, which occur ectopically in hyperparathyroid bone, are induced by SCF. Nontransformed osteoblasts and Saos2 or MG63 cells expressed SCF in response to PTH. Western analysis showed only large, cell-associated isoforms, M(r)s ~ 40-48 kD. Transfection of MG63 cells with plasmids expressing antisense SCF mRNA eliminated immunoreactive SCF. Sequencing osteoblast SCF cDNAs showed that exon 6 was omitted. mRNAs without exon 6 produce membrane-associated SCF isoforms in rodents, suggesting that human SCFs are processed similarly. The major osteoblastic SCF mRNA, ~ 5 kB, was augmented by PTH. Neither protein or mRNA was increased by vitamin D, however, 6-7 kB transcripts were predominant in other tissues but not detectable in osteoblasts. We conclude that osteoblasts express SCF in response to PTH, with mRNA and protein processing differences relative to other cells. SCF stimulates osteoclasts, suggesting that PTH-induced osteoblastic SCF functions to accelerate bone turnover. Mast cells may occur due to SCF overexpression at extreme PTH levels.
AB - We investigated stem cell factor (SCF) expression in osteoblasts because mast cells, which occur ectopically in hyperparathyroid bone, are induced by SCF. Nontransformed osteoblasts and Saos2 or MG63 cells expressed SCF in response to PTH. Western analysis showed only large, cell-associated isoforms, M(r)s ~ 40-48 kD. Transfection of MG63 cells with plasmids expressing antisense SCF mRNA eliminated immunoreactive SCF. Sequencing osteoblast SCF cDNAs showed that exon 6 was omitted. mRNAs without exon 6 produce membrane-associated SCF isoforms in rodents, suggesting that human SCFs are processed similarly. The major osteoblastic SCF mRNA, ~ 5 kB, was augmented by PTH. Neither protein or mRNA was increased by vitamin D, however, 6-7 kB transcripts were predominant in other tissues but not detectable in osteoblasts. We conclude that osteoblasts express SCF in response to PTH, with mRNA and protein processing differences relative to other cells. SCF stimulates osteoclasts, suggesting that PTH-induced osteoblastic SCF functions to accelerate bone turnover. Mast cells may occur due to SCF overexpression at extreme PTH levels.
KW - 1,25-Dihydroxyvitamin D
KW - Bone turnover
KW - c-kit
KW - Mast cell
KW - Splice variant
UR - http://www.scopus.com/inward/record.url?scp=0033599314&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033599314&partnerID=8YFLogxK
U2 - 10.1006/bbrc.1999.0260
DO - 10.1006/bbrc.1999.0260
M3 - Article
C2 - 10049787
AN - SCOPUS:0033599314
VL - 255
SP - 778
EP - 784
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -