title: Interleukin-11 induces osteoblast differentiation and acts synergistically with bone morphogenetic protein-2 in C3H10T1/2 cells.
abstract: Interleukin-11 (IL-11) is a pleiotropic cytokine that supports various types of hematopoietic cell growth and is involved in bone resorption. We report here the involvement of recombinant human IL-11 (rHuIL-11) in osteoblast differentiation in mouse mesenchymal progenitor cells, C3H10T1/2. rHuIL-11 alone increased alkaline phosphatase (ALP) activity and upregulated expression levels of osteocalcin (OC), bone sialo protein (BSP), and parathyroid hormone receptor (PTHR) mRNA. rHuIL-11 had no effect on expression of type II collagen, peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), adipocyte fatty acid-binding protein P2 (aP2), and myogenic MyoD protein (MyoD). Recombinant human bone morphogenetic protein (rHuBMP)-2 increased ALP activity and mRNA expression of these genes except for MyoD. The expression patterns of ALP activity and osteoblast-specific or chondrocyte-specific genes suggest that rHuIL-11 may be involved in early differentiation of osteoblasts at a step earlier than that which is affected by rHuBMP-2. In support of this hypothesis, combined treatment with rHuIL-11 and rHuBMP-2 synergistically increased ALP activity and mRNA expression of OC and type II collagen, rHuIL-11 also abrogated the increased levels of PPAR-gamma2, aP2 mRNA caused by rHuBMP-2. Our results suggest that rHuIL-11 alone and in combination with rHuBMP-2 can induce osteoblastic differentiation of progenitor cells and plays an important role in osteogenesis.
authors.affiliation: Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., Tsukuba, Ibaraki, Japan. suga.kazutaka@yamanouchi.co.jp
authors.forename: K
authors.initials: K
authors.lastname: Suga
authors.forename: M
authors.initials: M
authors.lastname: Saitoh
authors.forename: S
authors.initials: S
authors.lastname: Fukushima
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Nara
authors.forename: S
authors.initials: S
authors.lastname: Yasuda
authors.forename: K
authors.initials: K
authors.lastname: Miyata
mesh_terms: D000469:Alkaline Phosphatase / Q000187:drug effects*; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line / Q000166:cytology; D024043:Collagen Type II / Q000187:drug effects / Q000235:genetics; D004357:Drug Synergism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D017370:Interleukin-11 / Q000494:pharmacology*; D051379:Mice; D017570:MyoD Protein / Q000187:drug effects / Q000235:genetics; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010006:Osteoblasts / Q000166:cytology*; D015675:Osteocalcin / Q000187:drug effects* / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000235:genetics; D018016:Receptors, Parathyroid Hormone / Q000187:drug effects / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000187:drug effects* / Q000235:genetics; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins
chemical_list: C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D024043:Collagen Type II; C107608:FABP7 protein, human; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; C546871:IBSP protein, human; C546872:Ibsp protein, mouse; D058574:Integrin-Binding Sialoprotein; D017370:Interleukin-11; D017570:MyoD Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D018016:Receptors, Parathyroid Hormone; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; C499469:recombinant human bone morphogenetic protein-2; D015675:Osteocalcin; D000469:Alkaline Phosphatase