Biomedical subjects

T Taga

Publications and source records attributed to T Taga.

At least 73 records · Page 4Linked to original sources

PubMed1998

[Analysis of cytokine receptor function by gene manipulation].

As a tool to investigate physiological and pathological roles of cytokines, gene manipulation techniques have been applied to make mouse models having mutations in cytokine receptor genes. Functional pleiotropy and redundancy are two major characteristic features of cytokines. The latter feature is in part explained by the shared usage of a signal-transducing receptor component by several cytokine receptor complexes. In this article, studies with the help of gene manipulation techniques on a group of cytokine receptor complexes sharing the signal transducer, gp130, are reviewed. To investigate the in vivo roles of gp130, mice deficient for gp130 or having constitutively activated gp130 were made. Transgenic mice expressing a dominant-negative form of gp130 were produced as well. Observation from these mouse models and that from mice deficient for other gp130-related receptors and ligans are also reviewed in this article.

Animals↗

PubMed1998

[Studies of childhood non-Hodgkin's lymphoma--treatment results with the CCLSG NHL 960 protocol. Children's Cancer and Leukemia Study Group (CCLSG)].

We report here on the preliminary treatment findings of a CCLSG NHL 960 study that was initiated in March 1996. In this study, 37 patients with non-Hodgkin's lymphoma were assigned to 4 different treatment groups according to disease stage and histology: (1) localized disease; (2) advanced disease, lymphoblastic type; (3) advanced disease, large cell type; and (4) advanced disease, Burkitt type. The first three groups received the modified protocols of the NHL 890 study. Groups 1 and 3 received COPADM induction therapy (CPM, VCR, PRD, ADR, and MTX). After achieving remission, Group 1 received only maintenance therapy consisting of alternate administration of 7 drugs, while Group 3 received additional intensification therapy with combination chemotherapy consisting of MTX and Ara-C, followed by a maintenance phase involving the administration of 9 drugs. Group 2 received COPADL induction therapy (CPM, VCR, PRD, ADR, and LASP) and consolidation/intensification therapies followed by a maintenance phase. Group 4 received short-term intensive COPADM polychemotherapy. Twelve patients with localized with localized disease (stage I-II) and 25 patients with advanced disease (stage III-IV) were enrolled in this study. Except for 2 patients in the advanced disease stages who died earlier in the course of the study, all patients remained in remission.

Adolescent↗

PubMed1997

Simultaneous activation of signals through gp130, c-kit, and interleukin-3 receptor promotes a trilineage blood cell production in the absence of terminally acting lineage-specific factors.

We assessed the biologic role of signaling through gp130, a signal-transducing receptor (R) component, in human hematopoiesis in vitro. Although peripheral blood-derived CD34(+) cells ubiquitously expressed gp130 and interleukin-3 receptor alpha (IL-3Ralpha), IL-6Ralpha was only detected on 80% of these CD34(+) cells. We sorted CD34(+)IL-6R+ or CD34(+)IL-6R- cells and studied the effect on hematopoietic colony formation of signaling through gp130 activated by IL-6 or a combination of IL-6 and recombinant soluble human IL-6R (sIL-6R) in the presence or absence of stem cell factor (SCF ) and/or IL-3. Signals activated by SCF, IL-6, or IL-6/sIL-6R complex alone did not induce significant colony formation. However, a combination of IL-3, SCF, and IL-6/sIL-6R complex dramatically induced many neutrophil (colony-forming unit-granulocyte [CFU-G]), erythroid burst (burst-forming unit-erythrocyte [BFU-E]), erythrocyte-containing mixed (CFU-Mix), and megakaryocyte (CFU-Meg) colony formations when CD34(+)IL-6R- cells were used as the target. CFU-G colony formation induced by the three signals was more evident when CD34(+)IL-6R+ cells were used as the target. This distinct synergistic effect of the three different signals was confirmed by single-cell clone-sorting experiments. Moreover, colony formation (including CFU-G, BFU-E, CFU-Mix, and CFU-Meg) was observed even in the presence of neutralizing antibodies for granulocyte colony-stimulating factor, erythropoietin, and thrombopoietin (c-Mpl), whereas neutralizing antibodies for gp130, IL-6R, IL-3, and SCF partially or completely blocked the synergistic effect. The maturation of neutrophilic, erythroid, and megakaryocytic cells supported by the three signals in serum-free cultures was confirmed by immunostaining using anti-CD66b, antiglycophorin A, antihemoglobin alpha, and anti-CD41 monoclonal antibodies, respectively. In contrast, any two of the three signals were insufficient for effective blood cell production in the absence of maturation factors. These results suggest that simultaneous activation of the three signals through gp130, c-kit, and IL-3R can induce in vitro proliferation and differentiation of trilineage hematopoietic progenitors in the absence of terminally acting lineage-specific factors.

Animals↗

PubMed1997

Structure and function of a new STAT-induced STAT inhibitor.

The signalling pathway that comprises JAK kinases and STAT proteins (for signal transducer and activator of transcription) is important for relaying signals from various cytokines outside the cell to the inside. The feedback mechanism responsible for switching off the cytokine signal has not been elucidated. We now report the cloning and characterization of an inhibitor of STAT activation which we name SSI-1 (for STAT-induced STAT inhibitor-1). We found that SSI-1 messenger RNA was induced by the cytokines interleukins 4 and 6 (IL-4, IL-6), leukaemia-inhibitory factor (LIF), and granulocyte colony-stimulating factor (G-CSF). Stimulation by IL-6 or LIF of murine myeloid leukaemia cells (M1 cells) induced SSI-1 mRNA expression which was blocked by transfection of a dominant-negative mutant of Stat3, indicating that the SSI-1 gene is a target of Stat3. Forced overexpression of SSI-1 complementary DNA interfered with IL-6- and LIF-mediated apoptosis and macrophage differentiation of M1 cells, as well as IL-6 induced tyrosine-phosphorylation of a receptor glycoprotein component, gp130, and of Stat3. When SSI-1 is overexpressed in COS7 cells, it can associate with the kinases Jak2 and Tyk2. These findings indicate that SSI-1 is responsible for negative-feedback regulation of the JAK-STAT pathway induced by cytokine stimulation.

Amino Acid Sequence↗

PubMed1997

Enhancement of gp130-mediated tyrosine phosphorylation of STAT3 and its DNA-binding activity in dexamethasone-treated AIDS-associated Kaposi's sarcoma cells: selective synergy between dexamethasone and gp130-related growth factors in Kaposi's sarcoma cell proliferation.

The soluble IL-6R (slL-6R alpha)/IL-6 complex and oncostatin M (OM), which exert biologic activities through the signal-transducing protein gp130, are potent growth factors for AIDS-associated Kaposi's sarcoma (KS) cells. Clinical observations indicate that glucocorticoid therapy is a possible risk factor in KS; however, little is known of specific interactions in KS cells between glucocorticoid and gp130-related growth factors. We obtained evidence that dexamethasone (Dex), in a synergistic manner, enhances gp130-mediated growth of KS cells. Anti-gp130 Abs or the glucocorticoid antagonist RU-486 abolished this synergistic effect. In addition, Dex had additive but not synergistic effects on stimulation of KS cell growth with IL-1beta or TNF-alpha, the signals of which are not mediated through gp130. Immunoblot analysis revealed sIL-6R alpha/IL-6- or OM-induced tyrosine phosphorylation of a similar set of proteins in KS cells, and which was augmented significantly in Dex-treated KS cells. Stimulation of KS cells with sIL-6R alpha/IL-6 or OM induced rapid tyrosine phosphorylation of the transcription factor STAT3, and Dex significantly enhanced the accumulation of tyrosine-phosphorylated STAT3. Electrophoretic mobility shift assays showed sIL-6R alpha/IL-6- or OM-induced DNA-binding activity of STAT3 in KS cells, and Dex further increased this activity. Thus, Dex appears to participate in the gp130-STAT3 signaling and transcriptional events by enhancing STAT3 activation, thereby leading to selective synergistic stimulation of KS cell growth with Dex and the gp130-related growth factors.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Impairment of antigen-specific antibody production in transgenic mice expressing a dominant-negative form of gp130.

gp130 is a common signal-transducing receptor component for the interleukin 6 family of cytokines functioning in, for example, immune, hematopoietic, and nervous systems. In this study, to investigate the physiological functions of gp130 and to determine the pathological consequences of impaired gp130 signals, we have generated transgenic mice expressing a cytoplasmically truncated form of mouse gp130. Expression of this form of gp130 in lymphocytes significantly suppressed interleukin 6-induced tyrosine phosphorylation of endogenous gp130 and a downstream signaling molecule, signal transducer and activator of transcription 3, indicating that this form has a dominant negative function. In spite of the impaired gp130 signals, the development of lymphocytes in the transgenic mice appeared normal in terms of surface marker phenotypes. These mice, however, exhibited severe defects in antigen-specific antibody production of most immunoglobulin isotypes other than IgM after immunization with 2,4-dinitrophenol-conjugated ovalbumin. These results demonstrate in vivo that gp130 is essential for antigen-specific antibody production.

Actins↗

PubMed1997

Leptin receptor (OB-R) oligomerizes with itself but not with its closely related cytokine signal transducer gp130.

Leptin (OB) exerts weight-reducing effects in mice. The structure of the receptor for this factor, OB-R, is considerably similar to those of gp130, the common signal transducing receptor component for the interleukin-6 (IL-6) family of cytokines, and leukemia inhibitory factor receptor (LIFR). Since the IL-6 family of cytokines signal through gp130 homodimer or gp130/LIFR heterodimer, we have examined in this study the possible involvement of gp130 and LIFR in leptin signaling through OB-R. Leptin stimulation induces tyrosine phosphorylation of neither gp130 nor LIFR, while LIF stimulation does both. As examined by using two differently epitope-tagged OB-R molecules, the spontaneous homo-oligomerization of OB-R has been elucidated. Ba/F3 cells, which do not express gp130, are non-responsive to leptin and exhibit increased DNA synthesis in response to leptin after transfection of OB-R cDNA alone. OB-R appears to transduce the signal via its homo-oligomerization without interaction with gp130 or LIFR.

Animals↗

PubMed1997

Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6.

Vav is a hematopoietic cell-specific proto-oncogene. We show that interleukin-6 (IL-6) induces transient tyrosine phosphorylation of Vav in a human myeloma cell line, U266. A membrane-distal part of the cytoplasmic region of gp130 is critical for association between Vav and gp130, and the IL-6-induced tyrosine phosphorylation of Vav. Mitogen-activated protein kinase (MAPK) (p42MAPK or extracellular signal-regulated kinase 2 (Erk2)) is coprecipitated with Vav. MAPK activity in the anti-Vav immunoprecipitates is upregulated by IL-6 stimulation. Furthermore Vav is associated with Grb2 which is known as an adapter protein leading to Ras activation. The results imply that Vav may link gp130 activation to downstream MAPK activation in hematopoietic cells.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Overlapping and distinct signals through leptin receptor (OB-R) and a closely related cytokine signal transducer, gp130.

The structure of leptin receptor (OB-R) is highly homologous to that of gp130, the common signal transducing receptor component for the interleukin-6 family of cytokines. Based on this structural similarity, we examined signaling processes initiated by OB-R in comparison with those by gp130. Stimulation of either a long form of OB-R or gp130 led to tyrosine phosphorylation of STAT3, whereas stimulation of the truncated form of OB-R that is predominantly expressed in dbldb mice failed to do so. Stimulation of the long form OB-R did not induce tyrosine phosphorylation of a Src homology domain 2 containing protein tyrosine phosphatase, SHP-2, while stimulation of gp130 did. In contrast, activation of p42ERK2 is mediated by either the long form OB-R or gp130. Two closely related molecules, OB-R and gp130, thus appear to mediate overlapping but distinct signaling procedures.

Antigens, CD↗

PubMed1997

Cerebral infarction in incontinentia pigmenti: the first report of a case evaluated by single photon emission computed tomography.

A 2-month-old girl with incontinentia pigmenti presented with acute-onset right-handed focalized seizures and subsequent seizure generalization. Computed tomography, magnetic resonance imaging and single photon emission computed tomography results indicated that she had multiple cerebral infarctions. These findings suggest that incontinentia pigmenti should be included among the neurocutaneous syndromes associated with ischemic strokes in childhood. This is the first report of a case with incontinentia pigmenti associated with cerebral infarction evaluated by single photon emission computed tomography.

Brain↗

PubMed1997

Gp130 and the interleukin-6 family of cytokines.

Receptors for most interleukins and cytokines that regulate immune and hematopoietic systems belong to the class I cytokine receptor family. These molecules form multichain receptor complexes in order to exhibit high-affinity binding to, and mediate biological functions of, their respective cytokines. In most cases, these functional receptor complexes share common signal transducing receptor components that are also in the class I cytokine receptor family, i.e. gp130, common beta, and common gamma molecules. Interleukin-6 and related cytokines, interleukin-11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin-1 are all pleiotropic and exhibit overlapping biological functions. Functional receptor complexes for this interleukin-6 family of cytokines share gp130 as a component critical for signal transduction. Unlike cytokines sharing common beta and common gamma chains that mainly function in hematopoietic and lymphoid cell systems, the interleukin-6 family of cytokines function extensively outside these systems as well, e.g. from the cardiovascular to the nervous system, owing to ubiquitously expressed gp130. Stimulation of cells with the interleukin-6 family of cytokines triggers homo- or hetero-dimerization of gp130. Although gp130 and its dimer partners possess no intrinsic tyrosine kinase domain, the dimerization of gp130 leads to activation of associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors. This paper reviews recent progress in the study of the interleukin-6 family of cytokines and gp130.

Amino Acid Sequence↗

PubMed1997

Osteoclasts are present in gp130-deficient mice.

Interleukin (IL)-6, IL-11, leukemia inhibitory factor, and oncostatin M similarly induce osteoclast formation in cocultures of osteoblastic cells and bone marrow cells. These cytokines share a common signal transducer, gp130, which forms a receptor complex with the specific receptor for each cytokine. To investigate the role of gp130 in osteoclast development, we examined bone tissues in gp130-deficient and wild-type newborn mice of the ICR background. Soft x-ray radiographs and microfocus x-ray computed tomographs revealed that bone marrow cavities were present in tibiae and radii of both wild-type and gp130-deficient mice. Microfocus x-ray computed tomography and histological examination demonstrated a decrease in the amount of trabeculae at the metaphysial region in tibiae and radii of the gp130-deficient mice compared with the wild-type mice. The number ofosteoclasts in gp130-deficient mice was about double that in the wild-type mice. There were no apparent differences in the distributions of alkaline phosphatase-positive osteoblasts and the osteoid surface on the trabecular bone at the metaphysial region between the wild-type and gp130-deficient mice. The volume of mineralized trabecular bones was also decreased at mandibulae, accompanied by the increased number of osteoclasts in gp130-deficient mice compared with the wild-type and heterozygous mice. These results suggest that the formation of osteoclasts is not solely dependent on gp130 signaling, at least during fetal development. The osteoclastic bone resorption in gp130-deficient mice may be caused by the functional redundancy of bone-resorbing hormones and cytokines other than those of the IL-6 family.

Animals↗

PubMed1997

The signal transducer gp130 is shared by interleukin-6 family of haematopoietic and neurotrophic cytokines.

Receptors for many of the cytokines functioning in the haematopoietic system belong to the class I cytokine receptor family. In most cases these receptors share common signal transducing receptor components in the same family, which explains the functional redundancy of haematopoietic cytokines. Interleukin-6 and related cytokines, interleukin-11, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and cardiotrophin-1, are all pleiotrophic, from the haematopoietic to the nervous system, and exhibit overlapping biological activities. Receptors for these cytokines fall into the class I cytokine receptor family. Functional receptor complexes for the interleukin-6 family of cytokines share a membrane glycoprotein 130 (gp130) as a critical component for signal transduction. In these receptor complexes, gp130 and ligand-specific chains possess no intrinsic tyrosine kinase domain but are associated with cytoplasmic tyrosine kinases. Ligand stimulation triggers homo- or heterodimerization of gp130, leading to activation of the associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors. This paper reviews the recent progress in the study of gp130 and the background information from biomedical and biochemical viewpoints.

Animals↗

PubMed1997

[Long-term follow up of idiopathic thrombocytopenic purpura in childhood].

Sixty children with idiopathic thrombocytopenic purpura (ITP) were followed up for 15 to 208 months (mean 120 months) from their first visit. Of these 65% (39 cases) were suffering from acute ITP and 47% of the patients were male. Of the 21 patients with chronic ITP 43% (9 cases) entered remission within five years from the onset of the disease. Conversely patients with chronic ITP for more than five years did not enter remission. Four patients with chronic disease were diagnosed to be other diseases (i.e. three cases were aplastic anemia, the other was Evans' syndrome) after one to four years from the onset. Four patients with chronic ITP for more than five years from the onset are now doing well without any severe bleeding problems. The patients who recovered have had neither problems nor complications. None of the patients died of a cerebral hemorrhage or severe bleeding. We consider that long term outcome of ITP in childhood would be better than that of adult cases.

Child↗

PubMed1996

Analysis of interleukin 6 receptor and gp130 expressions and proliferative capability of human CD34+ cells.

We recently demonstrated that stimulation of gp130 by a combination of soluble interleukin 6 receptor (sIL-6R) and IL-6 but not IL-6 alone significantly stimulates the ex vivo expansion of primitive hematopoietic progenitors and the generation of erythroid cells from human CD34+ cells in the presence of stem cell factor (SCF). Here, we show that gp130 is found low positively on most CD34+ cells, whereas IL-6R is expressed on only 30-50% of these cells. Although most of the colonies generated from FACS-sorted CD34+IL-6R+ cells were granulocyte/macrophage (GM) colonies, CD34+IL-6R- cells gave rise to various types of colonies, including erythroid bursts, GM, megakaryocytes, and mixed colonies in methylcellulose culture with a combination of IL-6, sIL-6R, and SCF. Similar results were obtained in culture supplemented with a combination of IL-3, IL-6, SCF, granulocyte colony-stimulating factor, erythropoietin, and thrombopoietin. A limiting dilution analysis of long-term culture-initiating cells (LTC-IC) showed that the CD34+IL-6R- cells contained a larger number of LTC-IC than did the CD34+IL-6R+ cells. In a serum-free suspension of CD34+IL-6R- cells, the addition of sIL-6R to the combination of IL-6 and SCF dramatically increased the total and multipotential progenitors, whereas CD34+IL-6R+ cells failed to do so under the same conditions. These results indicate that most of the erythroid, megakaryocytic, and primitive human hematopoietic progenitors are included in the IL-6R- populations, and the activation of gp130 on these progenitors can be achieved by a complex of IL-6-sIL-6R, but not by IL-6 alone. The present culture system using IL-6, sIL-6R, and SCF may provide a novel approach for ex vivo expansion of human primitive hematopoietic progenitors.

Adult↗

PubMed1996

Thrombopoietin stimulates colony-forming unit-megakaryocyte proliferation and megakaryocyte maturation independently of cytokines that signal through the gp130 receptor subunit.

Thrombopoietin (Tpo), the ligand for the c-Mpl receptor, is a major regulator of megakaryopoiesis. Treatment of mice with Tpo raises the platelet count fourfold within a few days. Conversely, c-mpl knock-out mice have platelet counts that are 15% that of normal. The subunit structure of the c-Mpl receptor is not fully understood. Some cytokines that stimulate megakaryopoiesis (IL-6, IL-11, leukemia inhibitory factor, and oncostatin M) bind to receptors that use gp130 as a signal transduction subunit. For these reasons, we determined whether gp130 function was required for Tpo-induced signal transduction. Murine marrow cells were cultured in semi-solid media in the presence of Tpo or IL-3, with or without a neutralizing anti-gp130 monoclonal antibody (RX187) or a soluble form of c-Mpl receptor (soluble Mpl) that blocks Tpo bioactivity, and the numbers of colony-forming unit-megakaryocyte (CFU-Meg) colonies were counted on day 5. Murine marrow cells were also cultured in suspension under serum-free conditions for 5 days, and megakaryocyte DNA content was measured by flow cytometry, as an index of nuclear maturation. The addition of RX187 did not block Tpo-induced CFU-Meg colony growth nor CFU-Meg nuclear maturation in suspension culture. However, IL-3-induced CFU-Meg colony growth and megakaryocyte nuclear maturation decreased in the presence of RX187. Soluble Mpl completely ablated Tpo-induced CFU-Meg growth, and partially blocked IL-3-stimulated CFU-Meg growth. Thus the effects of Tpo on megakaryopoiesis in vitro do not depend on cytokines that signal through gp130. Furthermore, it is unlikely that gp 130 serves as a beta chain for the c-Mpl receptor, as Tpo signalling is unimpaired in the presence of RX187. In contrast, the effects of IL-3 on CFU-Meg growth are mediated in part through Tpo and through gp130-signalling cytokines.

Animals↗

PubMed1996

Coadministration of interleukin-6 (IL-6) and soluble IL-6 receptor delays progression of wobbler mouse motor neuron disease.

Interleukin-6 (IL-6), a multipotential cytokine, initiates signal transduction pathways similar to those of ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF). These molecules share the signal transducing receptor component, gp130. IL-6 triggers homodimerization of gp130, whereas CNTF and LIF induce heterodimerization of gp130 and LIF receptor. Although CNTF or LIF treatment attenuates motor deficits in wobbler mouse motor neuron disease (MND), neuroprotective effects of IL-6 on this animal have not yet been clarified. Here we studied whether simultaneous treatment with IL-6 and soluble IL-6 receptor (sIL-6R) can ameliorate symptomatic and neuropathological changes in wobbler mouse MND. After clinical diagnosis at postnatal age 3-4 weeks, wobbler mice received subcutaneous injection with human recombinant IL-6 (1.0 mg/kg), human sIL-6R (0.5 mg/kg), IL-6 + sIL-6R or vehicle, daily for 4 weeks in a blind fashion. Compared to vehicle, coadministration with IL-6 and sIL-6R potentiated grip strength, attenuated muscle contractures in the forelimbs, reduced denervation muscle atrophy and prevented degeneration of spinal motor neurons. Single administration with IL-6 or sIL-6R did not retard the symptomatic and neuropathological progression, although IL-6-treated mice did not raise anti-IL-6 antibodies. Treatment with IL-6 + sIL-6R, but not with IL-6 or sIL-6R alone delayed progression of wobbler mouse MND. Our results indicate that the neuroprotective mechanism for IL-6/sIL-6R on wobbler mouse MND differs from that of CNTF or LIF alone. We hypothesize that IL-6/sIL-6R complex may function on motor neurons through activation and homodimerization of gp130.

Animals↗

PubMed1996

The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures.

Interleukin (IL)-11 is a multifunctional cytokine whose role in osteoclast development has not been fully elucidated. We examined IL-11 production by primary osteoblasts and the effects of rat monoclonal anti-mouse glycoprotein 130 (gp130) antibody on osteoclast formation, using a coculture of mouse osteoblasts and bone marrow cells. IL-1, TNF alpha, PGE2, parathyroid hormone (PTH) and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) similarly induced production of IL-11 by osteoblasts, but IL-6, IL-4, and TGF beta did not. Primary osteoblasts constitutively expressed mRNAs for both IL-11 receptor (IL-11R alpha) and gp130. Osteotropic factors did not modulate IL-11R alpha mRNA at 24 h, but steady-state gp130 mRNA expression in osteoblasts was upregulated by 1 alpha,25(OH)2D3, PTH, or IL-1. In cocultures, the formation of multinucleated osteoclast-like cells (OCLs) in response to IL-11, or IL-6 together with its soluble IL-6 receptor was dose-dependently inhibited by rat monoclonal anti-mouse gp130 antibody. Furthermore, adding anti-gp130 antibody abolished OCL formation induced by IL-1, and partially inhibited OCL formation induced by PGE2, PTH, or 1 alpha,25(OH)2D3. During osteoclast formation in marrow cultures, a sequential relationship existed between the expression of calcitonin receptor mRNA and IL-11R alpha mRNA. Osteoblasts as well as OCLs expressed transcripts for IL-11R alpha, as indicated by RT-PCR analysis and in situ hybridization. These results suggest a central role of gp130-coupled cytokines, especially IL-11, in osteoclast development. Since osteoblasts and mature osteoclasts expressed IL-11R alpha mRNA, both bone-forming and bone-resorbing cells are potential targets of IL-11.

Animals↗