Biomedical subjects

T Kukita

Publications and source records attributed to T Kukita.

At least 19 recordsLinked to original sources

PubMed1999

A novel role of IL-15 in the development of osteoclasts: inability to replace its activity with IL-2.

IL-15 shares many activities with IL-2 on stimulating lymphocytes, hematopoietic progenitor cells, and macrophages. However, the role of IL-15 in osteoclastogenesis has not been elucidated. The recent finding of abundant IL-15 in rheumatoid arthritis synovial fluids suggested a possible role for this cytokine in the pathological destruction of bone and prompted us to determine whether IL-15 stimulates osteoclast formation. IL-15 stimulated the formation of multinucleated osteoclast-like cells in rat bone marrow cultures. In stroma-free cultures, IL-15 increased the number of mononuclear preosteoclast-like cells in the early stage of osteoclast formation. The stimulation was observed even after treatment with IL-15 for only 24 or 48 h of culture. Moreover, low IL-15 concentration (0.1 ng/ml) strongly increased the level of calcitonin receptor mRNA of mononuclear preosteoclast-like cells. Although IL-15 is known as a potent stimulator of TNF-alpha, its activity was not abolished by addition of anti-TNF-alpha Ab. Interestingly, IL-2 and IL-7, which utilize some IL-15R components, had no effect on osteoclast differentiation, but pretreatment with IL-2 or IL-7 of bone marrow cells before the addition of IL-15 inhibited the enhancing activity of IL-15. In summary, IL-15 has a novel activity to stimulate the differentiation of osteoclast progenitors into preosteoclasts, which cannot be replaced by IL-2 but may use components in common with IL-2R to mediate its effects.

Animals↗

PubMed1998

Localization of a novel inositol 1,4,5-trisphosphate binding protein, p130 in rat brain.

We have isolated a novel inositol 1,4,5-trisphosphate binding protein with molecular mass of 130 kDa (p130), homologous to phospholipase C-delta1 in amino acid sequence but with no catalytic activity. Here we report the expression and localization of p130 at the mRNA level in rat brain. Northern blotting showed that gene expression encoding p130 was most abundant in brain. Brain localization of p130-mRNA using an in situ hybridization technique revealed that in the cerebellum, the mRNA was detected in the granular cell and Purkinje cell layers, and cerebellar nuclei. In the cerebrum, the mRNA was localized in hippocampal pyramidal cells, dentate granule cells and pyramidal and/or granule cells of the cerebral cortex. The brain localization of p130-mRNA was similar to that of the beta-subtype of phospholipase C, indicating that p130 may be mainly involved in phospholipase Cbeta-mediated signaling.

Animals↗

PubMed1998

Laminin, a major basement membrane component of the blood vessel, as a negative regulator of osteoclastogenesis.

Laminin, the major basement membrane glycoprotein of the blood vessel, inducing many cellular responses, inhibited the differentiation of osteoclasts in a rat bone marrow culture system when immobilized on the surface of the culture wells, showing that laminin acts as a negative regulator of osteoclast differentiation in a nonsolubilized form. Laminin inhibited the process of preosteoclast formation from early progenitor cells in bone marrow. This laminin-mediated inhibition of osteoclastogenesis was blocked by the addition of laminin fragment YIGSR, indicating that the inhibitory effect of laminin was mediated via laminin receptors. This finding suggests a significant role of basement membrane laminin of the blood vessels as a negative regulator of osteoclastogenesis.

Acid Phosphatase↗

PubMed1998

Successful detection of active osteoclasts in situ by systemic administration of an osteoclast-specific monoclonal antibody.

Cell-surface proteins preferentially expressed on osteoclasts are thought to play important roles in the functional modulation of the osteoclasts. Recently, we found a novel cell-surface antigen designated Kat1-antigen (Kat1-Ag) specifically expressed on rat osteoclasts. It would be useful to regulate the functional activity of the osteoclasts directly via an osteoclast-specific antigen expressed on the cell surface of the osteoclasts. In order to establish the basis of such an application, in the present study we established a method for the direct detection of osteoclasts in situ by a systemic administration of the anti-Kat1-Ag monoclonal antibody (mAb Kat1) to rats, and we successfully detected functional osteoclasts in situ. Prior to performing in vivo experiments, we examined the reactivity of the mAb Kat1 to the isolated rat osteoclasts. Approximately 40-80% of the osteoclasts were reactive with mAb Kat1, suggesting that this mAb recognizes osteoclasts in a specific differentiation or functional state. Calcitonin treatment of osteoclast-like cells formed in vitro from bone marrow cells resulted in a conversion of Kat1-positive osteoclast-like cells into Kat1-negative multinucleated cells, showing the positive correlation between the Kat1-Ag expression and the potential bone-resorbing activity of osteoclasts. Administration of this lineage-specific mAb to the peritoneal cavity of newborn rats resulted in a successful recruitment of mAb Kat1 to the newly formed osteoclasts and functional osteoclasts in a highly specific manner. Detailed analysis by immunoelectron microscopy revealed that this mAb specifically bound to the basolateral side of the active osteoclasts, which were identified by their typical ruffled border and clear zone, whereas the mAb did not react to postfunctional osteoclasts. These findings demonstrate a high potential utility of mAb Kat1 in osteoclast-targeted regulation of bone remodeling.

Animals↗

PubMed1998

Expression of the mRNA for types I and II interleukin-1 receptors in dental tissues of mice during tooth development.

Interleukin-1 (IL-1) can exert its pleiotropic effects on nearly every tissue by binding to its cognate receptor. Two types of IL-1 receptors have been identified. A large number of cell types have been shown to possess IL-1 receptors in vitro and in vivo, but few studies have addressed the question of expression in dental tissues in vivo. Using in situ hybridization in normal newborn, young and adult mice, we have examined the cellular distribution of both types of IL-1 receptors in dental tissues. In the ameloblast layer of incisors and molars, the mRNA for the type I IL-1 receptor (IL-1RI) and the type II IL-1 receptor (IL-1RII) was detected at the presecretory stage. The expression level markedly increased and remained during amelogenesis at the secretory stage. At the maturation stage, however, the transcripts for both IL-1RI and -II mRNA disappeared. Expression of IL-1RI and -II mRNA was also observed in odontoblasts after crown morphogenesis had been completed, and continued in these cells during dentinogenesis. No transcripts were detected in stratum intermedium cells and other cells in dental follicle, stellate reticulum, dental papilla, or pulp. Additionally, both types of IL-1R mRNA were also detected in osteoclasts on surfaces of alveolar bone. These results demonstrated for the first time that enamel-secreting ameloblasts and dentine-secreting odontoblasts express IL-1RI and -II mRNA, suggesting that IL-1 plays a regulatory role in the function of ameloblasts and odontoblasts during tooth development of mice.

Age Factors↗

PubMed1998

IL-2-induced growth of CD8+ T cell prolymphocytic leukemia cells mediated by NF-kappaB induction and IL-2 receptor alpha expression.

The binding of interleukin-2 (IL-2) to its receptor on normal T cells induces nuclear expression of nuclear factor kappaB (NF-kappaB), activation of the IL-2 receptor (IL-2R) alpha chain gene, and cell proliferation. In the present study, the role of IL-2R signaling in the growth of CD8+ T cell prolymphocytic leukemia (T-PLL) cells has been investigated. Flow cytometry revealed that primary leukemia cells from a patient with CD8+ T-PLL expressed IL-2Ralpha and beta chains, and the cells showed a proliferative response and an increase in IL-2Ralpha expression on culture with exogeneous IL-2. Northern blot analysis failed to detect IL-2 mRNA, suggesting that IL-2 may act in a paracrine manner in vivo. Electrophoretic mobility-shift assays revealed that recombinant IL-2 increased NF-kappaB binding activity in nuclear extracts of the leukemia cells, and Northern blot analysis showed that IL-2 increased the abundance of mRNAs encoding the NF-kappaB components c-Rel and KBF1 in these cells. IL-2 binding analysis demonstrated that IL-2 markedly increased the number of low affinity IL-2Rs on the leukemia cells, without an effect on the number of high-affinity IL-2Rs. These results show that IL-2 is capable of inducing the nuclear expression of NF-kappaB in primary CD8+ T-PLL cells, and that this effect is mediated, at least in part, at a pretranslational level.

Blotting, Northern↗

PubMed1998

Involvement of lymphocyte function-associated antigen-1 and intercellular adhesion molecule-1 in osteoclastogenesis: a possible role in direct interaction between osteoclast precursors.

In our search for molecules involved in the process of osteoclast differentiation, we examined the surface phenotypes of the preosteoclast-like cells and osteoclast-like multinucleated cells (MNCs) formed in bone marrow cultures, using monoclonal antibodies recognizing different antigen molecules expressed on hematopoietic cells. Among these cell surface antigens, lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) were highly expressed on mononuclear cells in the cultures for forming preosteoclast-like mononuclear cells. The double detection of these two antigen molecules with osteoclast-specific antigen and with calcitonin receptor, using a fluorescence-activated cell sorter or autoradiography technique, revealed that LFA-1 and ICAM-1 were expressed on the preosteoclasts. The expression of ICAM-1 was detected on both preosteoclasts and osteoclast-like MNCs, whereas the expression of LFA-1 was restricted to preosteoclasts. We designed a peptide with the sequence of the binding site of ICAM-1 against the ligand LFA-1. In the whole bone marrow culture system for forming osteoclast-like MNCs, a significant inhibition of MNC formation was observed by the addition of this peptide. These results strongly suggest the involvement of an LFA-1/ICAM-1-interaction in osteoclastogenesis.

Animals↗

PubMed1998

Induction of abundant osteoclast-like multinucleated giant cells in adjuvant arthritic rats with accompanying disordered high bone turnover.

The development of an in vivo system for investigating osteoclast differentiation is important because molecular events occurring in vivo can be observed during the differentiation of the authentic osteoclasts. In adjuvant arthritic rats, an experimental model of human rheumatoid arthritis, extensive bone resorption is observed in the distal diaphysis of the tibia. In the area of extensive bone resorption, it is always accompanied with clusters of numerous multinucleated giant cells (MGCs) as well as bone-resorbing osteoclasts. Here we characterized the morphological properties of these MGCs with the use of enzymehistochemical and immunohistochemical techniques. Extensive destruction but also a marked formation of the inner and outer bone surfaces were the predominant features in the tibiae of such arthritic rats 4 weeks after the adjuvant injection. Numerous MGCs were frequently clustered in the bone marrow spaces located apart from the bone matrices. Although the MGCs lacked ruffled borders, these cells were rich in mitochondria and vacuoles. These multinucleated cells revealed a positive reaction for tartrate-resistant acid phosphatase but a negative reaction for non-specific esterase staining. Most of these MGCs expressed the Kat 1-antigen, an immunological marker specifically expressed on the cell surface of rat osteoclasts. In a dentin resorption experiment using a cluster of MGCs excised from the bone marrow tissues of the tibial distal diaphyses of rats with adjuvant arthritis, many resorption lacunae were formed on dentin slices after a 3-day culture. These results suggest that the majority of the MGCs are osteoclasts but not macrophage polykaryons.

Animals↗

PubMed1997

Expression and distribution of CC chemokine macrophage inflammatory protein-1 alpha/LD78 in the human brain.

Macrophage inflammatory protein (MIP)-1 alpha, also known as LD78, is a member of a family of chemokines which recruit leukocytes to sites of inflammation. We have shown by Northern blot analyses that MIP-1 alpha mRNA is expressed in several human tissues, including brain. To explore MIP-1 alpha distribution in brain tissue, we immunohistochemically examined brain tissues from 13 neuropsychiatric patients. Glial cells in the white matter of brain tissues from four patients with schizophrenia and one with manic depressive illness were MIP-1 alpha positive. Glial cells in the cortex from these patients were negative, except in one patient with schizophrenia in whom neurones as well as glial cells in the cortex stained positively for MIP-1 alpha. In situ hybridization showed that MIP-1 alpha mRNA was expressed in both neurones as well as glial cells in this patient. These results suggest a heterogeneous distribution of MIP-1 alpha in human brain.

Aged↗

PubMed1997

Granulocyte-colony stimulating factor induces differentiation and apoptosis of CD2, CD7 positive hybrid leukemia cells in vivo and ex vivo.

We report a case of a 70-year-old man with a hybrid leukemia treated successfully with granulocyte-colony stimulating factor (G-CSF) combined with a cytocine arabinoside regimen through the induction of differentiation of leukemic cells into monocytoid cells resulting in apoptosis. The leukemic cells demonstrated a TCR-gamma rearrangement, and expressed CD2, CD7, CD33 and G-CSF receptors but not CD11b on the cell surface nor non-specific esterase in cytoplasm. Several days following the administration of G-CSF, the cells with monocytoid characteristics such as CD11b and cytoplasmic non-specific esterase appeared in the peripheral blood replacing the blastic cells. The cells were shown to be derived from the same clone of the leukemic cell because of the identical TCR-gamma gene rearrangement. The short-term culture of leukemic cells with G-CSF induced the differentiation into a monocyte lineage, resulting in apoptosis. Although there is no denying the possibility that cytosine arabinoside is partly responsible, our results strongly suggest that G-CSF plays the main role in differentiation of leukemic cells into a monocyte lineage inducing apoptosis in vivo in this patient.

Aged↗

PubMed1997

Granulocyte-colony stimulating factor-induced proliferation of primary adult T-cell leukaemia cells.

Granulocyte-colony stimulating factor (G-CSF) is known to induce proliferation and differentiation of granulocyte progenitors, and is widely used to treat neutropenia induced by intensive chemotherapy for malignant lymphoma or adult T-cell leukaemia/lymphoma (ATL). G-CSF is thought not to stimulate malignant lymphoid cells. In the present study we examined the ability of G-CSF to induce in vitro growth of primary ATL cells from 14 patients (nine acute-type, two chronic-type and three lymphoma-type), and we analysed the in vivo counts of ATL cells in patients who received G-CSF for neutropenia. FACS analysis using phycoerythrin-labelled recombinant G-CSF demonstrated that ATL cells from 11/14 patients express some G-CSF receptor (G-CSFR), with a range between 5.4% and 87.3%. Cells expressing G-CSFR also expressed CD4. Reverse polymerase chain reaction (PCR) analysis demonstrated expression of G-CSFR messenger RNA in G-CSFR expressing cells. Leukaemic cells derived from seven (four acute-type, one chronic-type and two lymphoma-type) of the 14 patients proliferated in vitro in response to G-CSF, as measured by [3H]thymidine incorporation; maximum responses were at G-CSF concentrations of 10-100 ng/ml. Nine of 14 patients receiving rG-CSF for neutropenia were analysed retrospectively for ATL cell numbers. Four patients whose primary tumour cells proliferated in response to rG-CSF in vitro showed a significant increase in ATL cell count after administration of rG-CSF (P = 0.038), whereas five patients whose leukaemic cells did not proliferate in vitro showed no significant increase in ATL cell count. G-CSF can stimulate proliferation of ATL cells which may complicate therapy for this disease.

Aged↗

PubMed1997

Regulation of osteoclastogenesis by antisense oligodeoxynucleotides specific to zinc finger nuclear transcription factors Egr-1 and WT1 in rat bone marrow culture system.

Differentiation of osteoclasts is defined by the transcription factors expressed in response to bone microenvironments. In this work, we examined the effects of an expressional blockage of Egr-1 and/or WT1 on the differentiation of osteoclasts using specific antisense oligodeoxynucleotides (ODN). In a culture system forming preosteoclast-like cells (POC) from rat bone marrow cells depleted of marrow stromal cells, POC formation was markedly stimulated by the addition of Egr-1 antisense ODN compared to that in cultures in which sense ODN was added, whereas Egr-1 antisense ODN inhibited the formation of macrophage-like cells. The formation of multinucleated osteoclast-like cells was also stimulated by the addition of Egr-1 antisense ODN in whole bone marrow cultures. In contrast, WT1 antisense ODN did not affect POC formation induced by the treatment with Egr-1 antisense ODN; however, WT1 antisense ODN dramatically suppressed the formation of osteoclast-like multinucleated cells induced by the blockage of Egr-1 expression using Egr-1 antisense ODN. These data suggest that Egr-1 acts as the suppressor, not as the inducer, in osteoclastogenesis. The findings also suggested that WT1 could be involved in the multinucleation step of osteoclastogenesis, at least when Egr-1 expression was blocked.

Animals↗

PubMed1997

Macrophage inflammatory protein-1 alpha (LD78) expressed in human bone marrow: its role in regulation of hematopoiesis and osteoclast recruitment.

Human macrophage inflammatory protein-1 alpha (hMIP-1 alpha), also known as LD78, is a member of the chemokine/ intercrine family and an inhibitor of the proliferation of the hematopoietic stem cells in vitro. Using a specific monoclonal antibody, we observed significant localization of hMIP-1 alpha in eosinophilic myelocytes in human bone marrow. We further examined the expression of hMIP-1 alpha mRNA in human bone tissue by in situ hybridization. A high level of hMIP-1 alpha mRNA expression was detected in eosinophilic myelocytes in bone marrow, confirming these cells as the site of hMIP-1 alpha synthesis. hMIP-1 alpha mRNA expression was also detected in osteoblasts in the bone-remodeling sites, and osteoclasts were frequently observed in the vicinity of these osteoblasts. hMIP-1 alpha was also able to induce osteoclastogenesis on calcified matrices in the absence of any other osteotropic hormones. These results strongly suggest that hMIP-1 alpha is involved not only in the regulation of hematopoiesis but also in the modulation of bone remodeling.

Animals↗

PubMed1997

Vesnarinone exhibits antitumor effect against myeloid leukemia cells via apoptosis.

Vesnarinone is a positive inotropic agent used for treating congestive heart failure. We evaluated its ex vivo effects on myeloid leukemia cell lines and primary acute myelogenous leukemia cells. Vesnarinone inhibited the incorporation of radiolabeled thymidine by a myeloid cell line, HL60, in a dose-dependent manner at concentrations ranging from 0.1 to 30 microg/mL. A maximum 40% suppression was seen at a concentration of 10 microg/mL. Determination of viable cell counts by trypan blue dye exclusion method demonstrated vesnarinone to be cytocidal for HL60 cells. Vesnarinone induced DNA fragmentation as detected by electrophresis in HL60 cells after 72-hour culture; this effect was not inhibited by G-CSF. The apoptosis induced by vesnarinone was also detected by the in situ end-labeling method. Northern blot analysis showed a reduction of c-myc mRNA expression in HL60 cells by vesnarinone. However, immunostaining assay showed no change in the expression of Fas and Bcl-2 proteins. We next examined the effect of vesnarinone on primary myeloid leukemia cells derived from 10 patients: 3 cases of M1, 2 of M2, 3 of M3, 1 of M4, and 1 of M6, by the French-American-British classification. Vesnarinone inhibited the incorporation of thymidine in all cells, with a mean suppression of 58.1%. DNA electrophoresis showed induction of DNA fragmentation in cultured cells with vesnarinone for 72 hours in 8 of the 10 patients with primary leukemia. However, bone marrow mononuclear cells from healthy controls showed no growth suppression or DNA fragmentation in response to vesnarinone. These results suggest that vesnarinone may be useful in treating myeloid leukemia.

Adult↗

PubMed1997

Human T lymphotropic virus-type I Tax induction of CD21/Epstein-Barr virus receptor expression on T cells and its significance in leukemogenesis of adult T cell leukemia.

CD21, which is expressed on B cells, is also expressed on human T lymphotropic virus-type I (HTLV-I)-infected T cell lines. CD21 also serves as a receptor of Epstein-Barr virus (EBV). We evaluated the mechanism of CD21 induction on HTLV-I-infected T cells and its clinical significance in the leukemogenesis of adult T cell leukemia (ATL). CD21 induction was detected at very low levels in T cell lines (Jurkat and CEM cells), and in non- or low-Tax-producing HTLV-I-infected T cell lines (Oh13T, S1T, and Su9T01 cells). In contrast, marked induction of CD21 was detected in high-Tax-producing HTLV-I-infected T cell lines (K3T, F6T, and MT-2). A Jurkat T cell clone stably transfected with tax-expressing cDNA expressed a significant amount of CD21 on the cell surface. These results strongly suggest that HTLV-I Tax induces CD21 on T cells. On two-color analysis, CD21 expression was detected in CD4+ T cells of the primary ATL cells from a subset of patients, suggesting that EBV infection may be associated with the leukemogenesis of ATL, at least in part. However, no genome of EBV was detected in the genomic DNA of six HTLV-I-infected T cell lines or the primary ATL cells separated from all patients, indicating the irrelevance of EBV infection to ATL leukemogenesis.

DNA, Viral↗

PubMed1996

Relation of autonomous and interleukin-2-responsive growth of leukemic cells to survival in adult T-cell leukemia.

We examined autonomous and interleukin-2 (IL-2)-responsive growth activities of leukemic cells derived from peripheral blood, as well as several clinical manifestations, including serum lactate dehydrogenase (LDH) level, of 35 patients with adult T-cell leukemia (ATL) to determine whether these properties were related to prognosis. Growth activities were measured by [3H]-thymidine incorporation of the cells after 24 hours' culture with or without exogenous IL-2. Both autonomous and IL-2-responsive growth activities were higher in the patients than in healthy controls and were significantly correlated with each other (P < .0001, r = .956). Both higher growth activities were significantly associated with shorter survival times (P = .0042, r = .472 and P = .0117, r = .421, respectively). An increased serum LDH value was also significantly associated with shorter survival times (P = .0011, r = .530), but corrected calcium level, sex, white blood cell count, or age were not. These results strongly suggest that both growth activities of primary tumor cells, in addition to the serum LDH value, are prognostic determinants in ATL. We propose a new prognostic classification combining LDH values and autonomous growth activity into three groups: (1) high growth activity and high LDH; (2) high growth activity and low LDH, or low growth activity and high LDH; and (3) low growth activity and low LDH, which showed a significant relationship to survival time (P = .0014; the median survival time for each group was 39, 94, and 340 days, respectively).

Adult↗

PubMed1996

Osteoclast differentiation antigen.

Osteoclasts are the primary cells which perform bone resorption. The origin of these multinucleated giant cells is the haematopoietic stem cells. The differentiation pathway of the osteoclasts has so far been well studied and the cell-lineage of these bone resorbing cells is considered to be close but not identical to the monocytes/macrophages. Owing to the development of in vitro culture systems for evaluating osteoclast differentiation, it has been elucidated that various cytokines are involved in the differentiation of the osteoclasts. However, there is still ambiguity concerning the molecular mechanism of the differentiation of the osteoclasts. One approach for clarifying the molecular mechanism is to find unique antigen molecules involved in the process of osteoclast differentiation. In this review article, we introduce such immunological studies concerning osteoclast differentiation. We also refer to our recent establishment of a panel of monoclonal antibodies recognizing rat osteoclasts. One of the monoclonal antibodies recognizes cell surface antigen (Kat1-antigen) expressed on cells in osteoclast-lineage and not on monocytes/macrophages. Cross-linking of the cell surface antigen using this monoclonal antibody showed that the Kat1-antigen is the unique cell surface molecule involved in the regulation of the affinity of the calcitonin receptor and also involved in the modulation of bone resorption. In this review article, we overview, the current issues which should be elucidated for understanding the differentiation and activation of the osteoclasts. We further emphasize the utility of the immunological approach for solving these current target issues.

Animals↗

PubMed1996

Osteoclasts in normal and adjuvant arthritis bone tissues express the mRNA for both type I and II interleukin-1 receptors.

Osteoclasts are known to play a crucial role in both physiologic and pathologic bone resorption. Moreover, it is generally agreed that IL-1 has powerful effects on osteoclastic bone resorption, although the precise cellular sites and mechanisms by which IL-1 mediates osteoclastic bone resorption remain unclear. In particular, it is still controversial whether osteoclasts can respond to IL-1 directly. The expression of mRNA for type I IL-1 receptor (IL-1RI) and type II IL-1 receptor (IL-1RII) in osteoclasts was investigated in normal and inflammatory bone tissues by in situ hybridization to determine whether osteoclasts are the target cells for IL-1 and to elucidate the mechanism by which IL-1 induces osteoclastic bone resorption. For this study, normal tibiae were obtained from newborn, young, and adult mice and rats, and inflammatory bone tissues with bone destruction were obtained from adjuvant arthritis rat models. The results showed that (a) both IL-1 receptors (IL-1RI and -II) mRNA were expressed by osteoclasts in all tissue sections of normal tibiae; (b) at the stage of the adjuvant arthritis studied, the IL-1RI mRNA was the most predominant message in osteoclasts present in the area with serious cartilage and bone destruction, whereas the expression level of IL-1RII mRNA in these osteoclasts was weak; and (c) both IL-1RI and -II mRNA were expressed by osteoblasts, as well as by osteocytes localized in the osteoid. In addition, these messages were also expressed by chondrocytes, but the signals were not detected in the chondrocytes in the zones of hypertrophy and provisional calcification. Our present study demonstrates for the first time that mouse and rat osteoclasts express IL-1RI and -II mRNA, which suggest that a primary effect of IL-1 on osteoclasts may be one of the mechanisms by which IL-1 mediates normal bone remodeling and pathologic bone resorption in chronic inflammatory diseases.

Animals↗