Abstract
The parafollicular-cell (C-cell) hormone calcitonin (CT) can preserve or even augment skeletal mass by inhibiting osteoclast-mediated bone resorption. The possibility of an additional anabolic skeletal influence has also been raised: C cells might, via CT or other secretory products, affect osteoblast-mediated bone formation. The 57-residue amino-terminal procalcitonin cleavage peptide, N-proCT, has recently been identified in human and rat C cells, where it is made and secreted in equimolar amounts with CT. The coelaboration of N-proCT and CT and N-proCT's sequence conservation during evolution prompted us to investigate the potential skeletal bioactivity of N-proCT. We found that synthetic human N-proCT, at nanomolar concentrations, stimulated proliferation of normal and neoplastic human osteoblasts. At maximally effective doses, human N-proCT caused more than a 100% increase above the control rate of DNA synthesis, an effect comparable to the maximal growth effect of insulin, a potent mitogen for osteoblasts. Human N-proCT exerted a similar maximal mitogenic effect in chicken osteoblast cultures but at 100-fold greater concentrations than in human bone-cell cultures. The bone-cell action of N-proCT was potentiated with insulin with a > 200% increase in DNA synthesis at high insulin concentrations. In sharp contrast to these findings for N-proCT, the other bioactive C-cell peptides, CT and somatostatin, showed no mitogenic effects in human or chicken osteoblast cultures. Our results indicate that the action of N-proCT on cultured bone cells is separate from and potentiated by insulin, a known growth factor. Unlike insulin and related growth factors such as insulin-like growth factor I, N-proCT is not mitogenic in skin fibroblast cultures. We propose that N-proCT is a C-cell hormone that promotes bone formation via stimulatory actions on osteoblasts and preosteoblasts.
| Original language | English |
|---|---|
| Pages (from-to) | 9519-9523 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 86 |
| Issue number | 23 |
| DOIs | |
| State | Published - Dec 22 1989 |
| Externally published | Yes |
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Keywords
- C cells
- growth factors
- osteoblasts
- osteoporosis
- osteosarcoma
ASJC Scopus subject areas
- Genetics
- General
Cite this
Procalcitonin's amino-terminal cleavage peptide is a bone-cell mitogen. / Burns, D. M.; Forstrom, J. M.; Friday, K. E.; Howard, Guy; Roos, B. A.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 86, No. 23, 22.12.1989, p. 9519-9523.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Procalcitonin's amino-terminal cleavage peptide is a bone-cell mitogen
AU - Burns, D. M.
AU - Forstrom, J. M.
AU - Friday, K. E.
AU - Howard, Guy
AU - Roos, B. A.
PY - 1989/12/22
Y1 - 1989/12/22
N2 - The parafollicular-cell (C-cell) hormone calcitonin (CT) can preserve or even augment skeletal mass by inhibiting osteoclast-mediated bone resorption. The possibility of an additional anabolic skeletal influence has also been raised: C cells might, via CT or other secretory products, affect osteoblast-mediated bone formation. The 57-residue amino-terminal procalcitonin cleavage peptide, N-proCT, has recently been identified in human and rat C cells, where it is made and secreted in equimolar amounts with CT. The coelaboration of N-proCT and CT and N-proCT's sequence conservation during evolution prompted us to investigate the potential skeletal bioactivity of N-proCT. We found that synthetic human N-proCT, at nanomolar concentrations, stimulated proliferation of normal and neoplastic human osteoblasts. At maximally effective doses, human N-proCT caused more than a 100% increase above the control rate of DNA synthesis, an effect comparable to the maximal growth effect of insulin, a potent mitogen for osteoblasts. Human N-proCT exerted a similar maximal mitogenic effect in chicken osteoblast cultures but at 100-fold greater concentrations than in human bone-cell cultures. The bone-cell action of N-proCT was potentiated with insulin with a > 200% increase in DNA synthesis at high insulin concentrations. In sharp contrast to these findings for N-proCT, the other bioactive C-cell peptides, CT and somatostatin, showed no mitogenic effects in human or chicken osteoblast cultures. Our results indicate that the action of N-proCT on cultured bone cells is separate from and potentiated by insulin, a known growth factor. Unlike insulin and related growth factors such as insulin-like growth factor I, N-proCT is not mitogenic in skin fibroblast cultures. We propose that N-proCT is a C-cell hormone that promotes bone formation via stimulatory actions on osteoblasts and preosteoblasts.
AB - The parafollicular-cell (C-cell) hormone calcitonin (CT) can preserve or even augment skeletal mass by inhibiting osteoclast-mediated bone resorption. The possibility of an additional anabolic skeletal influence has also been raised: C cells might, via CT or other secretory products, affect osteoblast-mediated bone formation. The 57-residue amino-terminal procalcitonin cleavage peptide, N-proCT, has recently been identified in human and rat C cells, where it is made and secreted in equimolar amounts with CT. The coelaboration of N-proCT and CT and N-proCT's sequence conservation during evolution prompted us to investigate the potential skeletal bioactivity of N-proCT. We found that synthetic human N-proCT, at nanomolar concentrations, stimulated proliferation of normal and neoplastic human osteoblasts. At maximally effective doses, human N-proCT caused more than a 100% increase above the control rate of DNA synthesis, an effect comparable to the maximal growth effect of insulin, a potent mitogen for osteoblasts. Human N-proCT exerted a similar maximal mitogenic effect in chicken osteoblast cultures but at 100-fold greater concentrations than in human bone-cell cultures. The bone-cell action of N-proCT was potentiated with insulin with a > 200% increase in DNA synthesis at high insulin concentrations. In sharp contrast to these findings for N-proCT, the other bioactive C-cell peptides, CT and somatostatin, showed no mitogenic effects in human or chicken osteoblast cultures. Our results indicate that the action of N-proCT on cultured bone cells is separate from and potentiated by insulin, a known growth factor. Unlike insulin and related growth factors such as insulin-like growth factor I, N-proCT is not mitogenic in skin fibroblast cultures. We propose that N-proCT is a C-cell hormone that promotes bone formation via stimulatory actions on osteoblasts and preosteoblasts.
KW - C cells
KW - growth factors
KW - osteoblasts
KW - osteoporosis
KW - osteosarcoma
UR - http://www.scopus.com/inward/record.url?scp=0024326950&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024326950&partnerID=8YFLogxK
U2 - 10.1073/pnas.86.23.9519
DO - 10.1073/pnas.86.23.9519
M3 - Article
VL - 86
SP - 9519
EP - 9523
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 23
ER -