The effects of IGF-I and IGF-II on proliferation and differentiation of human osteoblasts and interactions with growth hormone.
BACKGROUND
We have previously shown that growth hormone (GH) consistently stimulates proliferation of human osteoblasts in vitro. In rat osteoblasts, GH augments the effects of insulin-like growth factor (IGF) I on cell proliferation and differentiation. We therefore investigated the effects of IGF-I and -II alone and in combination with GH on human osteoblasts in vitro.


METHODS
Human osteoblast-like cells (HOB) were established from trabecular explants (n = 18) and human marrow stromal cells (HMS) from marrow aspiration (n = 21). The cell cultures were stimulated with IGF-I or IGF-II (1, 10 or 100 ng mL-1) alone, in combination with hGH (100 ng mL-1) or after prestimulation with hGH.


RESULTS
IGF-I alone, in combination with hGH and after pretreatment with hGH, increased proliferation of HOB and HMS by 49-190% (P < 0.05-0.01). IGF-II alone, in combination with hGH and after pretreatment with hGH increased proliferation of HOB by 57-158% (P < 0.01). In HMS only IGF-II in combination with hGH and after prestimulation with hGH increased proliferation. IGF-I alone and in combination with hGH decreased alkaline phosphatase (AP) in both cell types. IGF-II did not affect AP in HOB, but increased AP in HMS, this effect was abolished by hGH. In HOB, collagen production (PICP) was increased by IGF-II but unaffected by IGF-I. In HMS, PICP was decreased by IGF-I and -II but increased by hGH. Co-stimulation further increased PICP.


CONCLUSIONS
IGF-I and -II exerted proliferative effects on both HOB and HMS. Co-stimulation with GH exhibited synergism in enhancing the proliferative response. In HMS prestimulation improved the proliferative response significantly. The effects of the IGFs on differentiation are more complex and dependent on cell maturation and of the IGF used.
Langdahl
B L
BL
Aarhus Bone and Mineral Research Group, University Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Aarhus C, Denmark. amtsbl@aau.dk
Kassem
M
M
Møller
M K
MK
Eriksen
E F
EF
D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D015675:Osteocalcin / Q000096:biosynthesis; D011347:Procollagen / Q000096:biosynthesis; D051381:Rats; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
D011347:Procollagen; D015675:Osteocalcin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D000469:Alkaline Phosphatase