Osteo-anabolic effects of human growth hormone with 22K- and 20K Daltons on human osteoblast-like cells.
Human growth hormone with 22,000 Dal (22K-hGH) stimulates proliferation and differentiation of osteoblasts as well as production of interleukin-6 in vitro and bone formation and remodeling in vivo. To investigate whether hGH isoform with 20Kd (20K-hGH), which accounts for 10% of circulating hGH, elicits similar metabolic effects on skeletal tissues, we studied the biological effects of 20K-hGH in cultured human osteoblast-like cells (HOB). HOB were obtained from trabecular bone explants and cultured in alpha-MEM supplemented with 10% FCS. In subconfluent cultures, 22K- and 20K-hGH stimulated [3H]thymidine incorporation by 62 +/- 27% and 63 +/- 23%, respectively (mean +/- SD, n=8, P>0.1). In confluent cultures, 22K- and 20K-hGH increased alkaline phosphatase activity by 38 +/- 23% and 41 +/- 23% (P>0.1), respectively, and increased the osteocalcin concentration in the presence of 10(-9) M 1,25-(OH)2D3 by 50% and 47% (P>0.1), respectively. Furthermore, both hGHs doubled the interleukin-6 (IL-6) concentration in the conditioned medium. RT-PCR analysis revealed that 22K- and 20K- hGH increased IL-6 gene expression 2.2 +/- 0.6 and 2.4 +/- 0.7 -fold, respectively. In summary, we have demonstrated that 20K-hGH elicits equipotent anabolic effects on HOB and stimulates to the same extent the production of IL-6, a cytokine which initiates osteoclastogenesis. These in vitro findings suggest that 22K- and 20K-hGH may equipotently stimulate bone remodeling and elicit anabolic effects on skeletal tissue when administered in vivo.
Wang
D S
DS
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Japan.
Sato
K
K
Demura
H
H
Kato
Y
Y
Maruo
N
N
Miyachi
Y
Y
D001846:Bone Development / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D019332:Endothelin-1 / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D019382:Human Growth Hormone / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008970:Molecular Weight; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000096:biosynthesis
D019332:Endothelin-1; D015850:Interleukin-6; D015675:Osteocalcin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D004247:DNA