Cytokine and hormonal stimulation of human osteosarcoma interleukin-11 production

Endocrinology. 1995 Feb;136(2):489-98. doi: 10.1210/endo.136.2.7835281.


Osteoclast-mediated bone resorption plays a crucial role in osseous remodeling. Osteoblasts are important regulators of this activity, in part through their ability to produce osteoclast-regulating soluble factors such as interleukin-6 (IL-6). IL-11 is a newly appreciated pleotropic cytokine whose spectrum of biological activities overlaps with that of IL-6. As a result, we hypothesized that osteoblasts are an important skeletal source of this cytokine. To test this hypothesis, we characterized the IL-11 production of unstimulated and stimulated SaOS-2 human osteosarcoma cells. Unstimulated cells produced modest amounts of IL-11. The osteotropic agents recombinant IL-1 (0.25-5 ng/ml), transforming growth factor-beta 1 (0.1-10 ng/ml), PTH (10(-8)-10(-11) M), and PTH-related peptide ((10(-8)-10-11 M) further increased SaOS-2 cell IL-11 protein production and messenger RNA accumulation. These stimulatory effects were dose and time dependent, and the IL-11 that was produced was bioactive, as demonstrated by its ability to stimulate the proliferation of T10D plasmacytoma cells. The protein kinase-C activator, 12-O-Tetra-decanoylphorbol 13-acetate, and a variety of cAMP agonists [forskolin, prostaglandin E1, prostaglandin E2, and (Bu)2AMP] also stimulated osteoblast IL-11 protein production and messenger RNA accumulation. In contrast, recombinant IL-4, recombinant interferon-gamma, and endotoxin did not stimulate SaOS-2 cells in a similar fashion. Importantly, the ability to produce IL-11 was not a unique property of SaOS-2 cells, because primary human trabecular bone osteoblasts also produced significant amounts of bioactive IL-11 when stimulated with transforming growth factor-beta 1. These studies demonstrate that appropriately stimulated human osteoblasts and osteoblast-like cells are potent producers of IL-11 and suggest that osteoblast-derived IL-11 may be an important component of the cytokine network mediating osteoblast-osteoclast communication in normal and pathological bone remodeling.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Bone Remodeling
  • Bone and Bones / metabolism
  • Child
  • Child, Preschool
  • Cyclic AMP / agonists
  • Cytokines / pharmacology*
  • Humans
  • Interleukin-11 / biosynthesis*
  • Middle Aged
  • Osteoblasts / metabolism*
  • Osteosarcoma / metabolism*
  • Parathyroid Hormone / pharmacology
  • Parathyroid Hormone-Related Protein
  • Plasmacytoma / metabolism
  • Plasmacytoma / pathology
  • Protein Kinase C / antagonists & inhibitors
  • Proteins / pharmacology
  • RNA, Messenger / biosynthesis*
  • Tumor Cells, Cultured


  • Cytokines
  • Interleukin-11
  • PTHLH protein, human
  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein
  • Proteins
  • RNA, Messenger
  • Cyclic AMP
  • Protein Kinase C