macrophage colony stimulating factor


Summary: A mononuclear phagocyte colony-stimulating factor (M-CSF) synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (RECEPTOR, MACROPHAGE COLONY-STIMULATING FACTOR).

Top Publications

  1. Chitu V, Stanley E. Colony-stimulating factor-1 in immunity and inflammation. Curr Opin Immunol. 2006;18:39-48 pubmed
    ..In several conditions, activation of macrophages involves a CSF-1 autocrine loop. In addition, secreted and cell-surface isoforms of CSF-1 can have differential effects in inflammation and immunity. ..
  2. Zauli G, Rimondi E, Corallini F, Fadda R, Capitani S, Secchiero P. MDM2 antagonist Nutlin-3 suppresses the proliferation and differentiation of human pre-osteoclasts through a p53-dependent pathway. J Bone Miner Res. 2007;22:1621-30 pubmed
  3. Schmitz G, Grandl M. Role of redox regulation and lipid rafts in macrophages during Ox-LDL-mediated foam cell formation. Antioxid Redox Signal. 2007;9:1499-518 pubmed
  4. Gowing G, Lalancette Hébert M, Audet J, Dequen F, Julien J. Macrophage colony stimulating factor (M-CSF) exacerbates ALS disease in a mouse model through altered responses of microglia expressing mutant superoxide dismutase. Exp Neurol. 2009;220:267-75 pubmed publisher
    b>Macrophage colony stimulating factor (M-CSF) is a cytokine that regulates the survival, proliferation and maturation of microglial cells...
  5. Nakano K, Okada Y, Saito K, Tanikawa R, Sawamukai N, Sasaguri Y, et al. Rheumatoid synovial endothelial cells produce macrophage colony-stimulating factor leading to osteoclastogenesis in rheumatoid arthritis. Rheumatology (Oxford). 2007;46:597-603 pubmed
    ..M-CSF produced by RAECs is involved in osteoclastogenesis from monocytes, migration and TRAP-positive MNC formation. ..
  6. Lari R, Fleetwood A, Kitchener P, Cook A, Pavasovic D, Hertzog P, et al. Macrophage lineage phenotypes and osteoclastogenesis--complexity in the control by GM-CSF and TGF-beta. Bone. 2007;40:323-36 pubmed
    ..It is proposed that the findings have particular relevance for the control of bone resorption in pathology, for example, in inflammatory lesions. ..
  7. Sakai H, Chen Y, Itokawa T, Yu K, Zhu M, Insogna K. Activated c-Fms recruits Vav and Rac during CSF-1-induced cytoskeletal remodeling and spreading in osteoclasts. Bone. 2006;39:1290-301 pubmed
    ..These data demonstrate that Vav and Rac lie downstream from activated PI3-K in CSF-1-treated osteoclasts and that Rac is required for CSF-1-induced cytoskeletal remodeling in these cells. ..
  8. Martinez F, Gordon S, Locati M, Mantovani A. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol. 2006;177:7303-11 pubmed
    ..Thus, transcriptome profiling reveals novel molecules and signatures associated with human monocyte-to-macrophage differentiation and polarized activation which may represent candidate targets in pathophysiology. ..
  9. Yang P, Kasai H, Xiao W, Zhao L, He L, Yamashita A, et al. Increased expression of macrophage colony-stimulating factor in ankylosing spondylitis and rheumatoid arthritis. Ann Rheum Dis. 2006;65:1671-2 pubmed

More Information


  1. Okazaki T, Ebihara S, Asada M, Yamanda S, Saijo Y, Shiraishi Y, et al. Macrophage colony-stimulating factor improves cardiac function after ischemic injury by inducing vascular endothelial growth factor production and survival of cardiomyocytes. Am J Pathol. 2007;171:1093-103 pubmed
    ..These results suggest M-CSF might be a novel therapeutic agent for ischemic heart disease. ..
  2. Hohensinner P, Kaun C, Rychli K, Niessner A, Pfaffenberger S, Rega G, et al. Macrophage colony stimulating factor expression in human cardiac cells is upregulated by tumor necrosis factor-alpha via an NF-kappaB dependent mechanism. J Thromb Haemost. 2007;5:2520-8 pubmed
    b>Macrophage colony stimulating factor (M-CSF) is a key factor for monocyte and macrophage survival and proliferation. M-CSF has been implicated in cardiac healing and repair after myocardial infarction...
  3. Ohno H, Uemura Y, Murooka H, Takanashi H, Tokieda T, Ohzeki Y, et al. The orally-active and selective c-Fms tyrosine kinase inhibitor Ki20227 inhibits disease progression in a collagen-induced arthritis mouse model. Eur J Immunol. 2008;38:283-91 pubmed
    ..Hence, inhibitors of the c-Fms tyrosine kinase might act as anti-inflammatory or anti-osteolytic agents against arthritis. ..
  4. Delgado C, Hoa N, Callahan L, Schiltz P, Jahroudi R, Zhang J, et al. Generation of human innate immune responses towards membrane macrophage colony stimulating factor (mM-CSF) expressing U251 glioma cells within immunodeficient (NIH-nu/beige/xid) mice. Cytokine. 2007;38:165-76 pubmed
    ..cells (PBMC) to cloned human HLA-A2+ U251 glioma cells (U251-2F11/TK) expressing membrane macrophage colony stimulating factor (mM-CSF) was investigated in vitro and in vivo...
  5. Xu W, Schlagwein N, Roos A, van den Berg T, Daha M, van Kooten C. Human peritoneal macrophages show functional characteristics of M-CSF-driven anti-inflammatory type 2 macrophages. Eur J Immunol. 2007;37:1594-9 pubmed
    ..We propose that pMPhi have the potential to maintain an anti-inflammatory condition in the peritoneal cavity. ..
  6. Tee M, Tesch G, Nikolic Paterson D, Brown F. Human peritoneal mesothelial cells isolated from spent dialysate fluid maintain contaminating macrophages via production of macrophage colony stimulating factor. Nephrology (Carlton). 2007;12:160-5 pubmed
    ..Supernatant obtained from these purified HPMC contained macrophage colony stimulating factor and induced proliferation of bone marrow-derived macrophages...
  7. Fujisaki K, Tanabe N, Suzuki N, Kawato T, Takeichi O, Tsuzukibashi O, et al. Receptor activator of NF-kappaB ligand induces the expression of carbonic anhydrase II, cathepsin K, and matrix metalloproteinase-9 in osteoclast precursor RAW264.7 cells. Life Sci. 2007;80:1311-8 pubmed
    ..These results indicate that the expression of CAII, cathepsin K, and MMP-9 in RAW264.7 cells is not induced by M-CSF, but by RANKL in the presence of IL-1alpha. ..
  8. Lin E, Li J, Gnatovskiy L, Deng Y, Zhu L, Grzesik D, et al. Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res. 2006;66:11238-46 pubmed
    ..Taken together, this study shows that tumor-associated macrophages play a key role in promoting tumor angiogenesis, an essential step in the tumor progression to malignancy. ..
  9. Bouyer P, Sakai H, Itokawa T, Kawano T, Fulton C, Boron W, et al. Colony-stimulating factor-1 increases osteoclast intracellular pH and promotes survival via the electroneutral Na/HCO3 cotransporter NBCn1. Endocrinology. 2007;148:831-40 pubmed
    ..This study provides the first evidence that osteoclasts express a CSF-1-regulated Na/HCO(3) cotransporter, which may play a role in cell survival. ..
  10. Douglass T, Driggers L, Zhang J, Hoa N, Delgado C, Williams C, et al. Macrophage colony stimulating factor: not just for macrophages anymore! A gateway into complex biologies. Int Immunopharmacol. 2008;8:1354-76 pubmed publisher
    b>Macrophage colony stimulating factor (M-CSF, also called colony stimulating factor-1) has traditionally been viewed as a growth/differentiation factor for monocytes, macrophages, and some female-specific tumors...
  11. Müller M, Berghoff M, Kobsar I, Kiefer R, Martini R. Macrophage colony stimulating factor is a crucial factor for the intrinsic macrophage response in mice heterozygously deficient for the myelin protein P0. Exp Neurol. 2007;203:55-62 pubmed
    ..We have previously shown that deficiency for macrophage colony stimulating factor (M-CSF) prevents an increase of the number of endoneurial macrophages and alleviates the mutants' ..
  12. Komano Y, Nanki T, Hayashida K, Taniguchi K, Miyasaka N. Identification of a human peripheral blood monocyte subset that differentiates into osteoclasts. Arthritis Res Ther. 2006;8:R152 pubmed
    ..Blockade of accumulation and activation of CD16- monocytes could therefore be a beneficial approach as an anti-bone resorptive therapy, especially for RA. ..
  13. Chen X, Liu H, Focia P, Shim A, He X. Structure of macrophage colony stimulating factor bound to FMS: diverse signaling assemblies of class III receptor tyrosine kinases. Proc Natl Acad Sci U S A. 2008;105:18267-72 pubmed publisher
    b>Macrophage colony stimulating factor (M-CSF), through binding to its receptor FMS, a class III receptor tyrosine kinase (RTK), regulates the development and function of mononuclear phagocytes, and plays important roles in innate immunity, ..
  14. Taylor J, Brownlow N, Domin J, Dibb N. FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor imatinib and mutation of Asp-802 to Val confers resistance. Oncogene. 2006;25:147-51 pubmed
    ..we report that imatinib is also an effective inhibitor of the closely related FMS receptor for macrophage colony stimulating factor and that mutation of Asp 802 of FMS to Val confers imatinib resistance...
  15. Ross F, Teitelbaum S. alphavbeta3 and macrophage colony-stimulating factor: partners in osteoclast biology. Immunol Rev. 2005;208:88-105 pubmed
    ..Signals from alphavbeta3 and/or c-Fms activate Syk and Vav3, originally defined by their function in lymphoid cells. Genetic depletion of either protein generates a strong bone phenotype, underscoring the promise of osteoimmunobiology. ..
  16. Gallet M, Mentaverri R, Sevenet N, Brazier M, Kamel S. Ability of breast cancer cell lines to stimulate bone resorbing activity of mature osteoclasts correlates with an anti-apoptotic effect mediated by macrophage colony stimulating factor. Apoptosis. 2006;11:1909-21 pubmed
    ..Blockade of M-CSF pathway could be thus of clinical value in the treatment of breast cancer related bone destruction. ..
  17. Conway J, McDonald B, Parham J, Keith B, Rusnak D, Shaw E, et al. Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580. Proc Natl Acad Sci U S A. 2005;102:16078-83 pubmed
    ..The ability of GW2580 to chronically inhibit CSF-1 signaling through cFMS kinase in normal and tumor cells in vivo makes GW2580 a useful tool in assessing the role of cFMS kinase in normal and disease processes. ..
  18. Ando W, Hashimoto J, Nampei A, Tsuboi H, Tateishi K, Ono T, et al. Imatinib mesylate inhibits osteoclastogenesis and joint destruction in rats with collagen-induced arthritis (CIA). J Bone Miner Metab. 2006;24:274-82 pubmed
    ..These findings suggest that imatinib mesylate could prevent joint destruction in patients with rheumatoid arthritis. ..
  19. Wang X, Kua H, Hu Y, Guo K, Zeng Q, Wu Q, et al. p53 functions as a negative regulator of osteoblastogenesis, osteoblast-dependent osteoclastogenesis, and bone remodeling. J Cell Biol. 2006;172:115-25 pubmed
    ..Thus, these results identify p53 as a novel regulator of osteoblast differentiation, osteoblast-dependent osteoclastogenesis, and bone remodeling. ..
  20. Himes S, Sester D, Ravasi T, Cronau S, Sasmono T, Hume D. The JNK are important for development and survival of macrophages. J Immunol. 2006;176:2219-28 pubmed
    ..This pattern of expression may underlie the novel role of JNK in macrophages. ..
  21. Clanchy F, Holloway A, Lari R, Cameron P, Hamilton J. Detection and properties of the human proliferative monocyte subpopulation. J Leukoc Biol. 2006;79:757-66 pubmed
    ..The phenotype and properties of the PM subpopulation were examined as a prelude to determining its role in disease using methods that can be applied to clarify human monocyte heterogeneity. ..
  22. Wang Y, Zeigler M, Lam G, Hunter M, Eubank T, Khramtsov V, et al. The role of the NADPH oxidase complex, p38 MAPK, and Akt in regulating human monocyte/macrophage survival. Am J Respir Cell Mol Biol. 2007;36:68-77 pubmed
    ..These findings demonstrate that ROS generated from the NADPH oxidase complex contribute to monocyte/macrophage survival induced by M-CSF via regulation of Akt and p38 MAPK. ..
  23. Varney M, Olsen K, Mosley R, Singh R. Paracrine regulation of vascular endothelial growth factor--a expression during macrophage-melanoma cell interaction: role of monocyte chemotactic protein-1 and macrophage colony-stimulating factor. J Interferon Cytokine Res. 2005;25:674-83 pubmed
  24. Gobert Gosse S, Bourgin C, Liu W, Garbay C, Mouchiroud G. M-CSF stimulated differentiation requires persistent MEK activity and MAPK phosphorylation independent of Grb2-Sos association and phosphatidylinositol 3-kinase activity. Cell Signal. 2005;17:1352-62 pubmed
    ..Therefore, M-CSF differentiation signaling in myeloid progenitor cells is mediated through persistent MEK activity but it is not strictly dependent upon Grb2-Sos interaction or PI 3-kinase activity. ..
  25. Kawata T, Tsutsui K, Kohno S, Kaku M, Fujita T, Tenjou K, et al. Amyloid beta protein deposition in osteopetrotic (op/op) mice is reduced by injections of macrophage colony stimulating factor. J Int Med Res. 2005;33:654-60 pubmed
    ..reduced number of macrophages and osteoclasts in various tissues, and have no systemic macrophage colony stimulating factor (M-CSF)...
  26. Paulus P, Stanley E, Schäfer R, Abraham D, Aharinejad S. Colony-stimulating factor-1 antibody reverses chemoresistance in human MCF-7 breast cancer xenografts. Cancer Res. 2006;66:4349-56 pubmed
    ..These studies support the paradigm of CSF-1 blockade in the treatment of solid tumors and show that anti-CSF-1 antibodies are potential therapeutic agents for the treatment of mammary cancer. ..
  27. Lee S, Lorenzo J. Cytokines regulating osteoclast formation and function. Curr Opin Rheumatol. 2006;18:411-8 pubmed
    ..In the future it is hoped that therapies that target cytokine actions may be used to reduce the effects of inflammatory diseases on bone, as well as to regulate normal bone physiology. ..
  28. Irvine K, Burns C, Wilks A, Su S, Hume D, Sweet M. A CSF-1 receptor kinase inhibitor targets effector functions and inhibits pro-inflammatory cytokine production from murine macrophage populations. FASEB J. 2006;20:1921-3 pubmed
    ..CSF-1R inhibitors such as CYC10268 provide a powerful tool to dissect the role of the CSF-1/CSF-1R signaling system in a range of biological systems and have potential for a number of therapeutic applications. ..
  29. Piva R, Ruggeri B, Williams M, Costa G, Tamagno I, Ferrero D, et al. CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood. 2008;111:2765-75 pubmed
  30. Cesar B, Abud A, de Oliveira C, Cardoso F, Gremski W, Gabardo J, et al. Activation of mononuclear bone marrow cells treated in vitro with a complex homeopathic medication. Micron. 2008;39:461-70 pubmed
    ..The response to Canova treatment indicates that it influences mononuclear differentiation and activation of bone marrow progenitor and stromal cells. ..
  31. Harman Boehm I, Bluher M, Redel H, Sion Vardy N, Ovadia S, Avinoach E, et al. Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab. 2007;92:2240-7 pubmed
    ..Macrophage infiltration into adipose tissue has been demonstrated to accompany obesity, with a potential preferential infiltration into intraabdominal vs. sc fat...
  32. Hozumi A, Osaki M, Goto H, Sakamoto K, Inokuchi S, Shindo H. Bone marrow adipocytes support dexamethasone-induced osteoclast differentiation. Biochem Biophys Res Commun. 2009;382:780-4 pubmed publisher
    ..NFkappa-B ligand (RANKL), Osteoprotegerin (OPG), and macrophage colony stimulating factor (M-CSF) expressions in bone marrow adipocytes with or without dexamethasone were examined...
  33. Mandal C, Ghosh Choudhury G, Ghosh Choudhury N. Phosphatidylinositol 3 kinase/Akt signal relay cooperates with smad in bone morphogenetic protein-2-induced colony stimulating factor-1 (CSF-1) expression and osteoclast differentiation. Endocrinology. 2009;150:4989-98 pubmed publisher
    ..Together, these data for the first time demonstrate that PI3K-dependent Akt activation regulates BMP-2-induced CSF-1 expression and provides a mechanism for osteoblastic cell-assisted osteoclast differentiation. ..
  34. Ghia J, Galeazzi F, Ford D, Hogaboam C, Vallance B, Collins S. Role of M-CSF-dependent macrophages in colitis is driven by the nature of the inflammatory stimulus. Am J Physiol Gastrointest Liver Physiol. 2008;294:G770-7 pubmed publisher
    ..These results indicate that M-CSF-dependent macrophages may play either a pro- or counterinflammatory role in acute experimental colitis, depending on the stimulus used to induce colitis. ..
  35. Alatery A, Basta S. An efficient culture method for generating large quantities of mature mouse splenic macrophages. J Immunol Methods. 2008;338:47-57 pubmed publisher
    ..Taken together, we describe and validate a method for generating Sp-Mphi in large quantities and high purity. These data should prove valuable in future studies characterizing the functions and maturation of Sp-Mphi. ..
  36. Gow D, Sester D, Hume D. CSF-1, IGF-1, and the control of postnatal growth and development. J Leukoc Biol. 2010;88:475-81 pubmed publisher
    ..Accordingly, CSF-1 may be considered a part of the GH/IGF-1 axis. ..
  37. Feng R, Desbordes S, Xie H, Tillo E, Pixley F, Stanley E, et al. PU.1 and C/EBPalpha/beta convert fibroblasts into macrophage-like cells. Proc Natl Acad Sci U S A. 2008;105:6057-62 pubmed publisher
    ..Our data suggest that it might become possible to induce the transdifferentiation of skin-derived fibroblasts into cell types desirable for tissue regeneration. ..
  38. Zarebski A, Velu C, Baktula A, Bourdeau T, Horman S, Basu S, et al. Mutations in growth factor independent-1 associated with human neutropenia block murine granulopoiesis through colony stimulating factor-1. Immunity. 2008;28:370-80 pubmed publisher
    ..This shared transcriptional pathway may provide new avenues for understanding SCN caused by mutations in other genes and for clinical intervention into human neutropenias. ..
  39. Waldo S, Li Y, Buono C, Zhao B, Billings E, Chang J, et al. Heterogeneity of human macrophages in culture and in atherosclerotic plaques. Am J Pathol. 2008;172:1112-26 pubmed publisher
  40. Lutter D, Ugocsai P, Grandl M, Orso E, Theis F, Lang E, et al. Analyzing M-CSF dependent monocyte/macrophage differentiation: expression modes and meta-modes derived from an independent component analysis. BMC Bioinformatics. 2008;9:100 pubmed publisher
    ..Moreover, recent research results like the involvement of proliferation associated cellular mechanisms during macrophage differentiation can be corroborated. ..
  41. Breitkreutz I, Raab M, Vallet S, Hideshima T, Raje N, Chauhan D, et al. Targeting MEK1/2 blocks osteoclast differentiation, function and cytokine secretion in multiple myeloma. Br J Haematol. 2007;139:55-63 pubmed
    ..The present study therefore provides a preclinical rationale for the evaluation of AZD6244 as a potential new therapy for patients with MM. ..
  42. Ko E, Amiri F, Pandey N, Javeshghani D, Leibovitz E, Touyz R, et al. Resistance artery remodeling in deoxycorticosterone acetate-salt hypertension is dependent on vascular inflammation: evidence from m-CSF-deficient mice. Am J Physiol Heart Circ Physiol. 2007;292:H1789-95 pubmed
  43. Wang T, Hanington P, Belosevic M, Secombes C. Two macrophage colony-stimulating factor genes exist in fish that differ in gene organization and are differentially expressed. J Immunol. 2008;181:3310-22 pubmed
    ..Thus MCSF has an important role in the immune system of fish as in mammals...
  44. Beck A, Espinosa I, Edris B, Li R, Montgomery K, Zhu S, et al. The macrophage colony-stimulating factor 1 response signature in breast carcinoma. Clin Cancer Res. 2009;15:778-87 pubmed publisher
    ..Our findings provide insight into macrophage biology and may facilitate the development of personalized therapy for patients most likely to benefit from CSF1-targeted treatments. ..
  45. Kubota Y, Takubo K, Shimizu T, Ohno H, Kishi K, Shibuya M, et al. M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. J Exp Med. 2009;206:1089-102 pubmed publisher
    ..Continuous M-CSF inhibition did not affect healthy vascular and lymphatic systems outside tumors. These results suggest that M-CSF-targeted therapy is an ideal strategy for treating ocular neovascular diseases and cancer. ..
  46. Yasui K, Yashiro M, Nagaoka Y, Manki A, Wada T, Tsuge M, et al. Thalidomide prevents formation of multinucleated giant cells (Langhans-type cells) from cultured monocytes: possible pharmaceutical applications for granulomatous disorders. Int J Immunopathol Pharmacol. 2009;22:707-14 pubmed
    ..Our results support thalidomides clinical efficacy in the treatment of chronic granulomatous disorders (granulomatosis)...
  47. Gartland A, Mason Savas A, Yang M, MacKay C, Birnbaum M, Odgren P. Septoclast deficiency accompanies postnatal growth plate chondrodysplasia in the toothless (tl) osteopetrotic, colony-stimulating factor-1 (CSF-1)-deficient rat and is partially responsive to CSF-1 injections. Am J Pathol. 2009;175:2668-75 pubmed publisher
  48. Marumo T, Hishikawa K, Yoshikawa M, Hirahashi J, Kawachi S, Fujita T. Histone deacetylase modulates the proinflammatory and -fibrotic changes in tubulointerstitial injury. Am J Physiol Renal Physiol. 2010;298:F133-41 pubmed publisher
    ..These findings suggest a potential of HDAC inhibition therapy aimed at reducing inflammation and fibrosis in tubulointerstitial injury...
  49. Loureiro R, Monaco K, Kearney J, Blickarz Durand C, Kirby S, Inamdar M, et al. csf1 is required for early embryonic macrophage development: characterization of the csf1(op)/csf1(op) mutation in ES cell-derived macrophages. Br J Haematol. 2008;141:739-42 pubmed publisher
  50. Qiu X, Zhu L, Pollard J. Colony-stimulating factor-1-dependent macrophage functions regulate the maternal decidua immune responses against Listeria monocytogenes infections during early gestation in mice. Infect Immun. 2009;77:85-97 pubmed publisher
    ..monocytogenes infection. These data suggest that the anti-Listeria responses in the maternal decidual tissue are dependent on CSF-1-regulated macrophages. ..
  51. Saha J, Xia J, Sandusky G, Chen Y, Gerlitz B, Grinnell B, et al. Study of plasma protein C and inflammatory pathways: biomarkers for dimethylnitrosamine-induced liver fibrosis in rats. Eur J Pharmacol. 2007;575:158-67 pubmed
  52. Aikawa Y, Katsumoto T, Zhang P, Shima H, Shino M, Terui K, et al. PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. Nat Med. 2010;16:580-5, 1p following 585 pubmed publisher
    ..Thus, in this subtype of AML, leukemia stem cells are contained within the CSF1R(high) cell population, and we suggest that targeting of PU.1-mediated upregulation of CSF1R expression might be a useful therapeutic approach. ..
  53. Wang Y, Nishida S, Elalieh H, Long R, Halloran B, Bikle D. Role of IGF-I signaling in regulating osteoclastogenesis. J Bone Miner Res. 2006;21:1350-8 pubmed
    ..IGF-I is required for maintaining the normal interaction between the osteoblast and osteoclast to support osteoclastogenesis through its regulation of RANKL and RANK expression. ..