Osteo-anabolic effects of human growth hormone with 22K- and 20K Daltons on human osteoblast-like cells

Endocr J. 1999 Feb;46(1):125-32. doi: 10.1507/endocrj.46.125.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Development / drug effects
  • Bone Remodeling / drug effects
  • Cells, Cultured
  • DNA / biosynthesis
  • Endothelin-1 / pharmacology
  • Gene Expression / drug effects
  • Human Growth Hormone / chemistry
  • Human Growth Hormone / pharmacology*
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Molecular Weight
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteocalcin / biosynthesis

Substances

  • Endothelin-1
  • Interleukin-6
  • Osteocalcin
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • DNA