• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Apr 1994; 93(4): 1516–1524.
PMCID: PMC294166

Interleukin-11: a new cytokine critical for osteoclast development.


Stromal cells of the bone marrow control the development of osteoclasts through the production of cytokines capable of promoting the proliferation and differentiation of hematopoietic progenitors. Moreover, the deregulated production of the cytokine IL-6 in the bone marrow mediates an increase in osteoclastogenesis after estrogen loss. IL-6, however, does not influence osteoclastogenesis in the estrogen-replete state, suggesting that other cytokines might be responsible for osteoclast development under physiologic circumstances. We report here that IL-11, a newly discovered cytokine that is produced by marrow stromal cells, induced the formation of osteoclasts exhibiting an unusually high degree of ploidy in cocultures of murine bone marrow and calvarial cells. Osteoclasts formed in the presence of IL-11 were capable of bone resorption, as evidenced by the formation of resorption pits, as well as the release of 45Ca from prelabeled murine calvaria. Further, an antibody neutralizing IL-11 suppressed osteoclast development induced by either 1,25-dihydroxyvitamin D3, parathyroid hormone, interleukin-1, or tumor necrosis factor; whereas inhibitors of IL-1 or TNF had no effect on IL-11-stimulated osteoclast formation. The effects of IL-11 on osteoclast development were blocked by indomethacin; more important, however, they were independent of the estrogen status of the marrow donors.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Metcalf D. The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells. Nature. 1989 May 4;339(6219):27–30. [PubMed]
  • Dorshkind K. Regulation of hemopoiesis by bone marrow stromal cells and their products. Annu Rev Immunol. 1990;8:111–137. [PubMed]
  • Shadduck RK, Waheed A, Greenberger JS, Dexter TM. Production of colony stimulating factor in long-term bone marrow cultures. J Cell Physiol. 1983 Jan;114(1):88–92. [PubMed]
  • Hattersley G, Kerby JA, Chambers TJ. Identification of osteoclast precursors in multilineage hemopoietic colonies. Endocrinology. 1991 Jan;128(1):259–262. [PubMed]
  • Kurihara N, Chenu C, Miller M, Civin C, Roodman GD. Identification of committed mononuclear precursors for osteoclast-like cells formed in long term human marrow cultures. Endocrinology. 1990 May;126(5):2733–2741. [PubMed]
  • Klein B, Wijdenes J, Zhang XG, Jourdan M, Boiron JM, Brochier J, Liautard J, Merlin M, Clement C, Morel-Fournier B, et al. Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia. Blood. 1991 Sep 1;78(5):1198–1204. [PubMed]
  • Roodman GD, Kurihara N, Ohsaki Y, Kukita A, Hosking D, Demulder A, Smith JF, Singer FR. Interleukin 6. A potential autocrine/paracrine factor in Paget's disease of bone. J Clin Invest. 1992 Jan;89(1):46–52. [PMC free article] [PubMed]
  • Girasole G, Jilka RL, Passeri G, Boswell S, Boder G, Williams DC, Manolagas SC. 17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. J Clin Invest. 1992 Mar;89(3):883–891. [PMC free article] [PubMed]
  • Jilka RL, Hangoc G, Girasole G, Passeri G, Williams DC, Abrams JS, Boyce B, Broxmeyer H, Manolagas SC. Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science. 1992 Jul 3;257(5066):88–91. [PubMed]
  • Passeri G, Girasole G, Jilka RL, Manolagas SC. Increased interleukin-6 production by murine bone marrow and bone cells after estrogen withdrawal. Endocrinology. 1993 Aug;133(2):822–828. [PubMed]
  • Paul SR, Yang YC, Donahue RE, Goldring S, Williams DA. Stromal cell-associated hematopoiesis: immortalization and characterization of a primate bone marrow-derived stromal cell line. Blood. 1991 Apr 15;77(8):1723–1733. [PubMed]
  • Paul SR, Bennett F, Calvetti JA, Kelleher K, Wood CR, O'Hara RM, Jr, Leary AC, Sibley B, Clark SC, Williams DA, et al. Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7512–7516. [PMC free article] [PubMed]
  • Kawashima I, Ohsumi J, Mita-Honjo K, Shimoda-Takano K, Ishikawa H, Sakakibara S, Miyadai K, Takiguchi Y. Molecular cloning of cDNA encoding adipogenesis inhibitory factor and identity with interleukin-11. FEBS Lett. 1991 Jun 3;283(2):199–202. [PubMed]
  • McKinley D, Wu Q, Yang-Feng T, Yang YC. Genomic sequence and chromosomal location of human interleukin-11 gene (IL11). Genomics. 1992 Jul;13(3):814–819. [PubMed]
  • Musashi M, Yang YC, Paul SR, Clark SC, Sudo T, Ogawa M. Direct and synergistic effects of interleukin 11 on murine hemopoiesis in culture. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):765–769. [PMC free article] [PubMed]
  • Tsuji K, Lyman SD, Sudo T, Clark SC, Ogawa M. Enhancement of murine hematopoiesis by synergistic interactions between steel factor (ligand for c-kit), interleukin-11, and other early acting factors in culture. Blood. 1992 Jun 1;79(11):2855–2860. [PubMed]
  • Musashi M, Clark SC, Sudo T, Urdal DL, Ogawa M. Synergistic interactions between interleukin-11 and interleukin-4 in support of proliferation of primitive hematopoietic progenitors of mice. Blood. 1991 Sep 15;78(6):1448–1451. [PubMed]
  • Teramura M, Kobayashi S, Hoshino S, Oshimi K, Mizoguchi H. Interleukin-11 enhances human megakaryocytopoiesis in vitro. Blood. 1992 Jan 15;79(2):327–331. [PubMed]
  • Hattersley G, Chambers TJ. Calcitonin receptors as markers for osteoclastic differentiation: correlation between generation of bone-resorptive cells and cells that express calcitonin receptors in mouse bone marrow cultures. Endocrinology. 1989 Sep;125(3):1606–1612. [PubMed]
  • Takahashi N, Yamana H, Yoshiki S, Roodman GD, Mundy GR, Jones SJ, Boyde A, Suda T. Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology. 1988 Apr;122(4):1373–1382. [PubMed]
  • Akatsu T, Takahashi N, Udagawa N, Sato K, Nagata N, Moseley JM, Martin TJ, Suda T. Parathyroid hormone (PTH)-related protein is a potent stimulator of osteoclast-like multinucleated cell formation to the same extent as PTH in mouse marrow cultures. Endocrinology. 1989 Jul;125(1):20–27. [PubMed]
  • Takahashi N, Akatsu T, Udagawa N, Sasaki T, Yamaguchi A, Moseley JM, Martin TJ, Suda T. Osteoblastic cells are involved in osteoclast formation. Endocrinology. 1988 Nov;123(5):2600–2602. [PubMed]
  • Akatsu T, Tamura T, Takahashi N, Udagawa N, Tanaka S, Sasaki T, Yamaguchi A, Nagata N, Suda T. Preparation and characterization of a mouse osteoclast-like multinucleated cell population. J Bone Miner Res. 1992 Nov;7(11):1297–1306. [PubMed]
  • Suda T, Takahashi N, Martin TJ. Modulation of osteoclast differentiation. Endocr Rev. 1992 Feb;13(1):66–80. [PubMed]
  • Starnes HF, Jr, Pearce MK, Tewari A, Yim JH, Zou JC, Abrams JS. Anti-IL-6 monoclonal antibodies protect against lethal Escherichia coli infection and lethal tumor necrosis factor-alpha challenge in mice. J Immunol. 1990 Dec 15;145(12):4185–4191. [PubMed]
  • Jilka RL. Parathyroid hormone-stimulated development of osteoclasts in cultures of cells from neonatal murine calvaria. Bone. 1986;7(1):29–40. [PubMed]
  • Boyde A, Ali NN, Jones SJ. Optical and scanning electron microscopy in the single osteoclast resorption assay. Scan Electron Microsc. 1985;(Pt 3):1259–1271. [PubMed]
  • Chambers TJ, McSheehy PM, Thomson BM, Fuller K. The effect of calcium-regulating hormones and prostaglandins on bone resorption by osteoclasts disaggregated from neonatal rabbit bones. Endocrinology. 1985 Jan;116(1):234–239. [PubMed]
  • Shinar DM, Rodan GA. Biphasic effects of transforming growth factor-beta on the production of osteoclast-like cells in mouse bone marrow cultures: the role of prostaglandins in the generation of these cells. Endocrinology. 1990 Jun;126(6):3153–3158. [PubMed]
  • Akatsu T, Takahashi N, Udagawa N, Imamura K, Yamaguchi A, Sato K, Nagata N, Suda T. Role of prostaglandins in interleukin-1-induced bone resorption in mice in vitro. J Bone Miner Res. 1991 Feb;6(2):183–189. [PubMed]
  • Dinarello CA. Interleukin-1 and its biologically related cytokines. Adv Immunol. 1989;44:153–205. [PubMed]
  • Yoshida H, Hayashi S, Kunisada T, Ogawa M, Nishikawa S, Okamura H, Sudo T, Shultz LD, Nishikawa S. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature. 1990 May 31;345(6274):442–444. [PubMed]
  • Felix R, Cecchini MG, Fleisch H. Macrophage colony stimulating factor restores in vivo bone resorption in the op/op osteopetrotic mouse. Endocrinology. 1990 Nov;127(5):2592–2594. [PubMed]
  • Wiktor-Jedrzejczak W, Bartocci A, Ferrante AW, Jr, Ahmed-Ansari A, Sell KW, Pollard JW, Stanley ER. Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4828–4832. [PMC free article] [PubMed]
  • Kodama H, Nose M, Niida S, Yamasaki A. Essential role of macrophage colony-stimulating factor in the osteoclast differentiation supported by stromal cells. J Exp Med. 1991 May 1;173(5):1291–1294. [PMC free article] [PubMed]
  • Shinar DM, Sato M, Rodan GA. The effect of hemopoietic growth factors on the generation of osteoclast-like cells in mouse bone marrow cultures. Endocrinology. 1990 Mar;126(3):1728–1735. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...