Kyushu University Academic Staff Educational and Research Activities Database
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Toshio Kukita Last modified date:2019.06.28

Professor / Oral Biological Sciences
Department of Dental Science
Faculty of Dental Science


Graduate School
Undergraduate School
Administration Post
Other


E-Mail
Phone
092-642-6300
Fax
092-642-6304
Academic Degree
Doctor of Dental Science (Kyushu University)
Country of degree conferring institution (Overseas)
No
Field of Specialization
Anatomy, Bone Cell Biology, Immunology, Oral Histology & Embryology
Total Priod of education and research career in the foreign country
00years00months
Outline Activities
Bone is a dynamic tissue in which continuous cycles of bone degradation (bone resorption) and bone formation occur at the surface of the bone. This biological process is known as Bone Remodeling. It is quite important to keep the balance between the amount of bone formation mediated by osteoblasts and that of bone resorption performed by osteoclasts in maintenance of healthy bone. Once we lose this balance, we suffer from the metabolic bone diseases, e.g. osteoporosis. Molecular mechanism of the bone remodeling is not fully understood. It is postulated that bone resorbing osteoclasts play a central role in Bone Remodeling. In other words, osteoclasts are required for the subsequent bone formation in the normal bone remodeling process. To know the detailed molecular mechanism of bone remodeling, we are focusing on searching unique cell surface molecules expressed on cell surface of osteoclasts and their precursors, which are involved in the regulatory process of bone remodeling. Furthermore, we are now focusing on the specific regulation of pathological bone destruction without affecting normal bone remodeling. For this purpose, we are extensively investigating the difference in the normal osteoclasts and pathologically activated osteoclasts (PAOC) in molecular level. It will be possible to regulate only the pathological bone destruction without affecting normal bone remodeling which is essential for keeping bone health.

Through these studies, it should be possible to regulate bone remodeling process in a highly specific manner. These studies provide abundant seeds creating novel medicine suitable for metabolic bone diseases and inflammatory bone destruction accompanying rheumatoid arthritis and periodontal disease.

The following are the list of studies currently performed in our laboratory.


1) Searching and identification of PAOC-specific cell surface molecules: Specific regulation of inflammatory bone destruction through PAPC-specific molecules.

2) Identification of cell surface molecule involved in membrane fusion among osteoclast precursors (one of the important steps in osteoclastogenesis): Regulation of osteoclastogenesis through this regulatory molecule.

3) Molecular basis of the coupling of osteoclasts and osteoblasts

4) Regulation of bone remodeling through osteoblast-specific cell surface molecules

5) Regulation of inflammatory bone destruction by mesenchymal stem cells

6) Regulation of bone metabolism through key molecules involved in the inert immunity

7) Regulation of bone remodeling by membrane tunneling nanotubes

8) Mechanism of bone metastasis of tumors

9) Regeneration of dentin: immunological approach
Research
Research Interests
  • Specific & Powerful Regulation of Pathological Bone Destruction which does not affect normal bone remodeling: Development of a Novel Strategy of the Next Generation
    keyword : pathological bone destruction, osteoclast, bone marrow, stem cell
    2012.04~2021.03.
  • 1)Molecular Mechanism of Osteoclast Differentiation and Activation 2)Specific Regulation of Inflammatory Bone Destruction 3)Mechanism of Hard Tissue Regeneration
    keyword : osteoclast. bone remodeling, hard tissue regeneration, regulation, tissue stem cell, monoclonal antibody
    2008.04~2013.03.
Academic Activities
Reports
1. Toshio Takano, Akiko Kukita, Yin-Ji Li, Takayoshi Yamaza, Toshio Kukita, Mesenchymal stem cells markedly suppress inflammatory bone destruction in rats with adjuvant-induced arthritis. , World Biomedical Frontier, 2014.12, Mesenchymal stem cells (MSCs) have potential to differentiate into multiple cell lineages. Recently, it was shown that MSCs also have anti-inflammatory and immunomodulatory functions. In this report, we investigated the regulatory function of MSCs in the development of inflammatory bone destruction in rats with adjuvant-induced arthritis (AA rats). MSCs were isolated from rat bone marrow tissues, expanded in the presence of basic FGF, and intraperitoneally injected into AA rats. MSC administration significantly suppressed inflammatory parameters: swelling score, swelling width, and thickness of hind paw. Radiographic evaluation indicated that MSC significantly suppressed bone destruction. Histological analysis showed that administration of MSCs markedly suppressed osteoclastogenesis in AA rats. To further delineate their effects on osteoclastogenesis, MSCs were added to in vitro bone marrow cultures undergoing osteoclastogenesis. MSCs significantly suppressed osteoclastogenesis in this system. Chemokine receptor expression in MSCs was assessed by RT-PCR, and a chemotactic assay was performed using a transwell culture system. MSCs showed significant chemotaxis to MIP-1α (CCL3) and SDF-1α (CXCL12), chemokines preferentially expressed in the area of inflammatory bone destruction. Furthermore, MSCs expressed IL-10 and osteoprotegerin, cytokines that suppress osteoclastogenesis. These data suggest that recruitment of MSC to the area of bone destruction in AA rats could suppress inflammatory bone destruction and raise the possibility that MSCs may have potential for the treatment of inflammatory bone destruction in arthritis.

PMID: 24395111.
2. Regulation of Osteoclastic Function through Cell Surface Receptors.
3. Modulation of ostoeclastogenesis by chemokines.
4. Toshio Kukita, Akiko Kukita, The new aspect of calcitonin escape phenomenon: A possible involvement of osteoclast differentiation antigen in the regulation of osteoclastogenesis ansd function of calcitonin receptor., Recent Research Developments in Endocrinology 2:347-355, 2001.02.
5. Toshio Kukita, Akiko Kukita, Osteoclast differentiation antigen., Histology and Histopathology 11:821-830, 1996.11.
6. Toshio Kukita, Akiko Kukita, The new aspect of calcitonin escape phenomenon: A possible involvement of osteoclast differentiation antigen in the regulation of osteoclastogenesis and function of calcitonin receptor, Recent Research Developments in Endocrinology, 2:347-355, 2001.01.
Papers
1. Badawy T, Kyumoto-Nakamura Y, Uehara N, Zhang J, Sonoda S, Hiura H, Yamaza T, Kukita A, Kukita T., Osteoblast lineage-specific cell-surface antigen (A7) regulates osteoclast recruitment and calcification during bone remodeling., Lab Invest., 10.1038/s41374-018-0179-4., 99(6):866-884. doi: 10.1038/s41374-018-0179-4. Epub 2019 Feb 11., 2019.06, Bone remodeling is a continuous process characterized by highly coordinated cell-cell interactions in distinct multi-cellular units. Osteoclasts, which are specialized bone resorbing cells, play a central role in bone remodeling. Although the RANKL/ RANK axis determines the gross number of osteoclasts present in bone tissue, detailed molecular events regulating bone remodeling related to osteoclast recruitment, initiation of bone remodeling, and coupling of bone resorption and bone formation are still ambiguous. We hypothesized that osteoblast-specific cell-surface molecules contribute to the molecular modulation of bone remodeling. Therefore, we searched for regulatory cell-surface molecules expressed on osteoblasts by use of B-cell hybridoma technology. We obtained a monoclonal antibody A7 (A7 MAb) highly specific to cells of osteoblast-lineage. Here we describe the expression pattern and possible role of A7 antigen specifically recognized by A7 MAb. In vitro, A7 antigen was expressed on cell-surface of osteoblasts and osteoblast-like bone marrow stromal cells. In vivo, A7 antigen was detected in a subset of bone surface osteoblasts and in osteocytes, with a typical cell membrane expression pattern. Tissue array analysis showed only a limited expression of A7 antigen in osteocytes close to the bone surface. Immunoblotting and immunoprecipitation analysis showed that A7 antigen is a lineage-specific cell-surface protein with an approximate molecular weight of 45 KDa. Cross-linking of cell-surface A7 antigen in cultures of osteoclastogenesis showed stimulation of osteoclast formation. Marked suppression of calcification in primary osteoblast cultures was observed when A7 antigen was cross-linked with anti-A7 antigen MAb, A7 MAb. These data suggest that A7 antigen regulates recruitment of osteoclasts and triggering of calcification. A7 antigen may be an important molecule involved in the precise regulation of bone remodeling.
.
2. Shiratori T, Kyumoto-Nakamura Y, Kukita A, Uehara N, Zhang J, Koda K, Kamiya M, Badawy T, Tomoda E, Xu X, Yamaza T, Urano Y, Koyano K, Kukita T. J Immunol., IL-1β Induces Pathologically Activated Osteoclasts Bearing Extremely High Levels of Resorbing Activity: A Possible Pathological Subpopulation of Osteoclasts, Accompanied by Suppressed Expression of Kindlin-3 and Talin-1., The Journal of Immunology, doi: 10.4049/jimmunol.1602035. Epub 2017 Nov 15., 200(1):218-228., 2018.01, As osteoclasts have the central roles in normal bone remodeling, it is ideal to regulate only the osteoclasts performing pathological bone destruction without affecting normal osteoclasts. Based on a hypothesis that pathological osteoclasts form under the pathological microenvironment of the bone tissues, we here set up optimum culture conditions to examine the entity of pathologically activated osteoclasts (PAOCs). Through searching various inflammatory cytokines and their combinations, we found the highest resorbing activity of osteoclasts when osteoclasts were formed in the presence of M-CSF, receptor activator of NF-κB ligand, and IL-1β. We have postulated that these osteoclasts are PAOCs. Analysis using confocal laser microscopy revealed that PAOCs showed extremely high proton secretion detected by the acid-sensitive fluorescence probe Rh-PM and bone resorption activity compared with normal osteoclasts. PAOCs showed unique morphology bearing high thickness and high motility with motile cellular processes in comparison with normal osteoclasts. We further examined the expression of Kindlin-3 and Talin-1, essential molecules for activating integrin β-chains. Although normal osteoclasts express high levels of Kindlin-3 and Talin-1, expression of these molecules was markedly suppressed in PAOCs, suggesting the abnormality in the adhesion property. When whole membrane surface of mature osteoclasts was biotinylated and analyzed, the IL-1β–induced cell surface protein was detected. PAOCs could form a subpopulation of osteoclasts possibly different from normal osteoclasts. PAOC-specific molecules could be an ideal target for regulating pathological bone destruction..
3. Norihisa Uehara, Akiko Kukita, Yukari Kyumoto-Nakamura, Takayoshi Yamaza, Hisataka Yasuda, Toshio Kukita, Osteoclast-derived Laminin-332 is a novel negative regulator of osteoclastogenesis in bone microenvironments, Laboratory Investigation, 10.1038/labinvest.2017.55, (in press) (E-pub), 2017.06.
4. LI YINJI, Akiko Kukita, Yukari Kyumoto-Nakamura, Toshio Kukita, Extremely High Expression of Antisense RNA for Wilms' Tumor-1 in Active Osteoclasts: Suppression of WT1 Protein Expression during Ostoeclastogenesis., American Journal of Pathology 186(9)2317-2325, 2016, doi.org/10.1016/j.ajpath.2016.05.005, 186(9)2317-2325, 2016, 2016.08, Wilms' tumor 1 (WT1), a zinc-finger transcription regulator of the early growth response family, identified as the product of a tumor suppressor gene of Wilms' tumors, bears potential ability to induce macrophage differentiation in blood cell differentiation. Herein, we examined the involvement of WT1 in the regulation of osteoclastogenesis. We detected a high level of WT1 protein expression in osteoclast precursors; however, WT1 expression was markedly suppressed during osteoclastogenesis. We examined expression of WT1 transcripts in bone tissue by RNA in situ hybridization. We found a high level of antisense transcripts in osteoclasts actively resorbing bone in mandible of newborn rats. Expression of antisense WT1 RNA in mandible was also confirmed by Northern blot analysis and strand-specific RT-PCR. Overexpression of antisense WT1 RNA in RAW-D cells, an osteoclast precursor cell line, resulted in a marked enhancement of osteoclastogenesis, suggesting that antisense WT1 RNA functions to suppress expression of WT1 protein in osteoclastogenesis. High level expression of antisense WT1 RNA may contribute to commitment to osteoclastogenesis, and may allow osteoclasts to maintain or stabilize their differentiation state..
5. Peng-Fei Qu, Akiko Kukita, Yin-Ji Li, Kanako Moriyama, Lin Lei, Toshio Kukita, Involvement of deoxyadenosine and adenosine deaminase in the Methotrexate-induced suppression of inflammatory bone destruction., "Adenosine Receptors: Pharmacology, Functions and Therapeutic Aspects" NOVA hardcover edited collection (by selected invited only), NOVA Science Publisher, NY. USA (in press), 143-164, 2015.03.
6. Toshio Kukita, Akira Takahashi, Jing-Qi Zhang, Akiko Kukita, Membrane Nanotube Formation in Osteoclastogenesis, Methods in Molecular Biology, 10.1007/978-1-4939-2703-6, 1313, 193-202, 2015.05.
7. Kanako Moriyama, Akiko Kukita, LI YINJI, Norihisa Uehara, Zhang Jing-Qi, Ichiro Takahashi, Toshio Kukita, Regulation of osteoclastogenesis through Tim-3: A possible involvement of Tim-3/galectin-9 system in the modulation of inflammatory bone destruction., Laboratory Investigation , 10.1038/labinvest.2014.107., 94, 11, 1200-1211, 2014.11, Galectins are a unique family of lectins bearing one or two carbohydrate recognition domains (CRDs) that have the ability to bind molecules with β-galactoside-containing carbohydrates. It has been shown that galectins regulate not only cell growth and differentiation but also immune responses, as well as inflammation. Galectin-9, a tandem repeat type of galectin, was originally identified as a chemotactic factor for eosinophils, and is also involved in the regulatory process of inflammation. Here, we examined the involvement of galectin-9 and its receptor, T-cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3), in the control of osteoclastogenesis and inflammatory bone destruction. Expression of Tim-3 was detected in osteoclasts and its mononuclear precursors in vivo and in vitro. Galectin-9 markedly inhibited osteoclastogenesis as evaluated in osteoclast precursor cell line RAW-D cells and primary bone marrow cells of mice and rats. The inhibitory effects of galectin-9 on osteoclastogenesis was negated by the addition of β-lactose, an antagonist for galectin binding, suggesting that the inhibitory effect of galectin-9 was mediated through CRD. When galectin-9 was injected into rats with adjuvant-induced arthritis, marked suppression of bone destruction was observed. Inflammatory bone destruction could be efficiently ameliorated by controlling the Tim-3/galectin-9 system in rheumatoid arthritis.

PMID:
25264706
[PubMed - indexed for MEDLINE].
8. Toshio Takano, Yin-Ji Li, Akiko Kukita, Takayoshi Yamaza, Hisayuki Nomiyama, Yasunori AYUKAWA, Kanako Moriyama, Norihisa Uehara, Kiyoshi Koyano, Toshio Kukita, Mesenchymal stem cells markedly suppress inflammatory bone destruction in rats with adjuvant-induced arthritis, Laboratory Investigation, doi:10.1038/labinvest.2013.152, 94, 286-296, 94, 286-296, 2014.01.
9. Akira Takahashi, Akiko Kukita, Li YinJi, King-qi Zhang, Hisayuki Nomiyama, Takayoshi Yamaza, Yasunori Ayukawa, kiyoshi koyano, Toshio Kukita, Tunneling Nanotube Formation is Essential for the Regulation of Osteoclastogenesis, Journal of Cellular Biochemistry, 10.1002/jcb.24433, 114, 6, 1238-1247, 2013.06.
10. Junpei Teramachi, Akiko Kukita, Seiji Nakamura, Toshio Kukita, Adenosine blocks aminopterin-induced suppression of osteoclast differentiation, Journal of Bone and Mineral Metabolism, 10.1007/s00774-012-0388-7, 31, 1, 64-70, 2013.01.
11. Kukita A, Kukita T, Li Y-J, Yoshida H., Miyamoto H., Gay S., Pessler F., Shoubuike T., The Transcription Factor FBI-1/OCZF/LRF is Expressed in Osteoclasts and Regulates RANKL-induced Osteoclast Formation In vitro and In vivo. , Arthritis & Rheumatism, 10.1002/art.30455, 63, 9, 2744-2754, 2011.09, Abstract
OBJECTIVE: Since transcription factors expressed in osteoclasts are possible targets for regulation of bone destruction in bone disorders, we investigated the expression of the transcription factor FBI-1/OCZF/LRF (in humans, factor that binds to inducer of short transcripts of human immunodeficiency virus type 1; in rats, osteoclast-derived zinc finger; in mice, leukemia/lymphoma-related factor) in patients with rheumatoid arthritis (RA), and assessed its role in osteoclastogenesis in vivo.

METHODS: Expression of FBI-1/OCZF was investigated in subchondral osteoclasts in human RA and in rat adjuvant-induced arthritis (AIA) using immunostaining and in situ hybridization, respectively. Transgenic mice overexpressing OCZF (OCZF-Tg) under the control of the cathepsin K promoter were generated, and bone mineral density and bone histomorphometric features were determined by peripheral quantitative computed tomography, calcein double-labeling, and specific staining for osteoclasts and osteoblasts. LRF/OCZF expression and the consequence of LRF inhibition were assessed in vitro with RANKL-induced osteoclast differentiation.

RESULTS: FBI-1/OCZF was detected in the nuclei of osteoclasts in rat AIA and human RA. RANKL increased the levels of LRF messenger RNA and nuclear-localized LRF protein in primary macrophages. In OCZF-Tg mice, bone volume was significantly decreased, the number of osteoclasts, but not osteoblasts, was increased in long bones, and osteoclast survival was promoted. Conversely, inhibition of LRF expression suppressed the formation of osteoclasts from macrophages in vitro.

CONCLUSION: FBI-1/OCZF/LRF regulates osteoclast formation and apoptosis in vivo, and may become a useful marker and target in treating disorders leading to reduced bone density, including chronic arthritis..
12. Junpei Teramachi, Akiko Kukita, Seiji Nakamura, Toshio Kukita, Adenosine abolishes MTX-induced suppression of osteoclastogenesis and inflammatory bone destruction in adjuvant-induced arthritis., Laboratory Investigation, 91, 719-731, 2011.05, Methotrexate (MTX) is widely utilized for the treatment of patients with rheumatoid arthritis (RA); however, recent observation of the MTX-resistant patients proposed some difficulty in MTX-dependent therapeutic approach for RA. To access cellular events related to MTX resistance in RA in respect to inflammatory bone destruction, we investigated on an involvement of the potent inflammatory mediator adenosine in the regulation of osteoclastogenesis and inflammatory bone destruction. In rats with adjuvant-induced arthritis (AA rats), MTX efficiently suppressed bone destruction when it was administrated within 3 days after adjuvant injection, while it could not suppress inflammatory bone destruction if MTX was injected at the time of onset of inflammation (at day 10 after adjuvant injection). Time-course change in the level of plasma adenosine of AA rats was estimated by use of high-performance liquid chromatography and elucidated that adenosine level was markedly elevated till 10 days after adjuvant injection. In vitro bone marrow culture system for evaluating osteoclastogenesis, MTX markedly suppressed osteoclastogenesis in a stromal cell-dependent manner. This MTX-induced suppression of osteoclastogenesis was abrogated by the addition of adenosine. MTX suppressed the expression of mRNA for the receptor activator NF-κB ligand (RANKL), but it did not suppress the expression of osteoprotegerin (OPG). The addition of MTX and adenosine together markedly suppressed the level of OPG expression. Abolishment of MTX action by adenosine was significantly blocked by MRS1754, a highly selective antagonist for the A(2b) adenosine receptor (A(2b)AR), but not by caffeine, an antagonist for A₁, A(2a), A₃ AR (A₁AR, A(2a)AR, and A₃AR), which suggests that adenosine acts through A(2b)AR. Immunohistochemical studies showed abundant expression of A(2b)AR in cells localized in the bone-bone marrow boundary of the distal tibia in AA rats but not in control rats. When adenosine was injected in the ankle joints of MTX-treated AA rats, the suppressive effects of MTX on bone destruction was abolished. The current data therefore suggest that upregulation of adenosine production abolished the suppressive effect of MTX on osteoclastic bone destruction. Involvement of the adenosine-A(2b)AR system may explain MTX resistance in RA..
13. Li YinJi, Akiko Kukita, Junpei Teramachi, Kengo Nagata, Hiro Take, Toshio Kukita, A possible suppressive role of galectin-3 in up-regulated osteoclastogenesis accompanying adjuvant-induced arthritis in rats. , Laboratory Investigation , 89:26-37,2009., 2009.01.
14. Q-Y. Tang, Toshio Kukita, Akiko Kukita, Tadahiko Iijima, Regulation of osteoclastogenesis by Simon extracts composed of caffeic acid and related compounds: successfull suppression of bone destruction accompanied with adjuvant-induced arthritis in rats., Histochemistry and Cell Biology, 125:215-225., 2006.05.
15. T.Nakamura, T.Kukita, T.Shoubuike, K.Nagata, Z.Wu. T.Hotokebuchi, O.Kohashi, A.Kukita, Inhibition of Histone Deacetylase Suppresses Osteoclastogenesis and Bone Destruction by Inducing IFN-β Production., The Journal of Immunology, 175, 9, 5809-5816, 175(9):5809-5816, 2005.11.
16. M.Ohishi, Y.Matsumura, D.Aki, R.Mashima, K.Taniguchi, T.Kobayashi, T.Kukita, Y.Iwamoto, A.Yoshimura, SOCS1 and SOCS3 regulate osteoclastogenesis in the presence of inflammatory cytokines., The Journal of Immunology, 174, 3024-3031, 174:3024-3031., 2005.03.
17. T.Kukita, N.Wada, A.Kukita, T.Kakimoto, F.Sandra, K.Toh, K.Nagata, T.Iijima, M.Horiuchi, H.Matsusaki, K.Hieshima, O.Yoshie, H.Nomiyama, RANKL-induced DC-STAMP is essential for osteoclastogenesis., The Journal of Experimental Medicine, 10.1084/jem.20040518, 200, 7, 941-946, 200:941-946, 2004.09.
18. Kazuko Toh, Toshio Kukita, Hiro Take, Akiko Kukita, Ferry Sandra, Q-Y. Tang, Hisayuki Nomiyama, Tadahiko Iijima, A Possible Involvement of MIP-1α in the Recruitment of Osteoclast Progenitors to the Distal Tibia in Rats with Adjuvant-induced Arthritis, Laboratory Investigation, 10.1038/labinvest.3700132, 84, 1092-1102, 84:1092-1102, 2004.01.
19. T. Watanabe, T. Kukita, A. Kukita, N.Wada, K.Toh, K.Nagata, H.Nomiyama, T.Iijima, Direct stimulation of osteoclastogenesis by MIP-1α: Evidence obtained from studies using RAW264 cell clone highly responsive to RANKL., J.Endocrinology, 10.1677/joe.0.1800193, 180, 1, 193-201, 180(1):193-201, 2004.01.
20. M.M.Rahman, A.Kukita, T.Kukita, T.Shobuike, T.Nakamura, O.Kohashi, Two histon deacetylase inhibitor, trichostatin A and sodium butyrate, suppress differentiation of osteoclasts but not into macrophages., Blood, 10.1182/blood-2002-08-2622, 101, 9, 3451-3459, 101:3451-3459, 2003.01.
21. T.Kukita, A.Kukita, T.Watanabe, T.Iijima, Osteoclast differentiation antigen, distinct from receptor activator of nuclear factor kappa B, is involved in osteoclastogenesis under calcitonin-regulated conditions., J.Endocrinology, 10.1677/joe.0.1700175, 170, 1, 175-183, 170:175-183, 2001.01.
22. A.Kukita, T.Kukita, M.Ouchida, H.Maeda, H.Yatsuki. O.Kohashi., Osteoclast-derived zinc finger (OCZF) protein with POZ domain, a possible transcriptional repressor, is involved in osteoclastogenesis., Blood, 94, 6, 1987-1997, 94:1987-1997, 1999.01.
23. Y.Ogata, A.Kukita, T.Kukita, M.Komine, A.Miyahara, S.Miyazaki, O.Kohashi, A novel role of IL-15 in the development of osteoclasts: Inability to replace its activity with IL-2., The Journal of Immunology, 162, 5, 2754-2760, 162:2754-2760., 1999.01.
24. T.Kukita, A.Kukita, L.Xu, H.Maeda, T.Iijima., Successful detection of active osteoclasts in situ by systemic administration of an osteoclast-specific monoclonal antibody., Calcif.Tissue Int., 10.1007/s002239900506, 63, 2, 148-153, 63:148-153, 1998.01.
25. T.Kukita, K.Hata, A.Kukita, T.Iijima., Laminin, a major basement membrane component of the blood vessel, as a negative regulator of osteoclastogenesis., Calcif.Tissue Int., 10.1007/s002239900504, 63, 2, 140-142, 63:140-142, 1998.01.
26. H.Harada, T.Kukita, A.Kukita, Y.Iwamoto, T.Iijima., Involvement of lymphocyte function-associated antigen-1 and intercellular adhesion molecule-1 in osteoclasto- genesis: A possible role in direct interaction between osteoclast precursors., Endocrinology, 10.1210/en.139.9.3967, 139, 9, 3967-3975, 139:3967-3975, 1998.01.
27. Kukita T., Kukita A., Harada H., and Iijima T. , Regulation of osteoclastogenesis by antisense oligodeoxynucleotides specific to zinc finger nuclear transcription factors Egr-1 and WT1 in rat bone marrow culture system., Endocrinology , 10.1210/en.138.10.4384, 138, 10, 4384-4389, 1997.10.
28. Kukita T., Nomiyama H., Ohmoto Y., Kukita A., Shuto T., Hotokebuchi T., Sugioka Y., Miura R., and Iijima T. , Macrophage inflammatory protein-1 alpha (LD78) expressed in human bone marrow: its role in regulation of hematopoiesis and osteoclast recruitment. , Lab. Invest. 76:399-406 (IF; 4.479), 76, 3, 399-406, 1997.03.
29. Kukita T., Kukita A., Nagata K., Maeda H., Kurisu K., Watanabe T., and Iijima T. , Novel cell-surface Ag expressed on rat osteoclasts regulating the function of the calcitonin receptor.
, J. Immunol. , 153, 11, 5265-5273, 153:5265-5273 , 1994.12.
30. Otsuka T., Nomiyama H., Yoshida H., Kukita T., Kuhara S., and Sakaki Y. , Complete nucleotide sequence of the 26S rRNA gene of Physarum polycephalum: its significance in gene evolution.
, Proc. Natl. Acad. Sci. U. S. A. , 10.1073/pnas.80.11.3163, 80, 11, 3163-3167, 80:3163-3167
, 1983.06.
31. Kukita T., Sakaki Y., Nomiyama H., Otsuka T., Kuhara S., and Takagi Y. , Structure around the 3' terminus of the 26S ribosomal RNA gene of Physarum polycephalum.
, Gene , 16, 1-3, 309-315, 16:309-315
, 1981.12.
Presentations
1. Tamer Badawy, Yukari Kyumoto-Nakamura, Norihisa Uehara, Akiko Kukita, Toshio Kukita, Osteoblast-Specific Cell-Surface Antigen Regulating Osteoclastogenesis and Calcification: A Possible Unique Modulator of Bone Remodeling, American Society for Bone and Mineral Research (ASMBR) 2018 Annual Meeting, 2018.09.
2. Badwy Tamer, 久本 由香里、上原 範久、張 旌旗、山座 孝義、久木田 明子、久木田 敏夫, Osteoblast Lineage-Specific Cell-Surface Antigen Regulating Osteoclastogenesis and Calcification: A Possible New Player in Bone Remodeling, 第60回 歯科基礎医学会, 2018.09.
3. Tamer Badawy, Yukari-Kyumoto-Nakamura, Norihisa Uehara, Jingqi Zhang, Hidenobu Hiura, Akiko Kukita, Toshio Kukita, Novel Osteoblast-Lineage Specific Cell-Surface Antigen Possibly Regulation Osteoclastogenesis and Calcification, 第36回 日本骨代謝学会, 2018.07.
4. Shiratori T, Kukita A, Kyumoto-Nakamura Y, Uehara N, Zhang J, Koda K, Kamiya M, Badawy, Xu X, Yamaza T, Urano Y, Koyano K, Kukita T., Osteoclasts formed under stimulation by IL-1β possess extremely high ability to secrete Protons and to resorb dentin with abnormal adhesiveness, imaged by pH-sensitive fluorescence probes., American Society for Bone and Mineral Rsearch, 2017.09.
5. Kanako Moriyama, Akiko Kukita, Ichiro Takahashi, Toshio Kukita, A Possible Regulation of Osteoclast Differentiation by Galectin-9, International Bone and Mineral Society, 2013.06.
6. Osteoclasts express high level of anti-sense RNA for Zn-finger transcription factor WT1: Maintenance of the osteoclast differentiation states by Egr-1 and anti-sense RNA for WT1..
7. Osteoclast surface antigen involved in the induction of calcitonin-escape phenomenon.
Membership in Academic Society
  • International Bone and Minaral Society (IBMS)
  • Molecular Biology Society of Japan
  • Japanese Society of Bone and Mineral Metabolism
  • Japanese Association for Oral Biology
  • Japanese Association of Anatomists
Educational
Educational Activities
Oral Histology (Lecture): I am teaching students of Faculty of Dental Science in Kyushu University details about histology of tooth tissues and periodontal tissues involving enamel, dentin, cementum, pulp, gingiva and periodontal ligament as well as the histology of oral mucous membrane and salivary gland. I always doing efforts to explain histology from the aspect of developmental biology, in other words, I explain how each tissue structures seen in oral tissues were formed during morphogenesis of the human body.

Oral Cell Biology (Lecture): I introduce research world to students of Faculty of Dental Science in Kyushu University. After showing the overview of cell growth and differentiation as well as recent development in regenerative medicine, I explain bone metabolism especially about osteoclast cell biology.

Practice in histology: I teach students of Faculty of Dental Science in Kyushu University about histology of the digestive tissues involving esophagus, stomach, small intestine, large intestine, liver and pancreas.

Basic Biology II(Lecture): As the lecture of Basic Biology II to students of Kyushu University, I pick up some topics in the current life science (regenerative medicine, cancer specific medicine et al.) and explain each topic with illustrating basic knowledges in biology.

Oral Histology (Kyushu Dental College): I teach overview of bone metabolism to students of Kyushu Dental College.

Since 1999 President of Ice Hockey Club of Kyushu University
Other Educational Activities
  • 2009.11, Kyudai Festival Special Lecture: As a special event in the festival of Kyushu University, based on the selection by students in Ito campus, I was invited by students as a special speaker of the Special Lecture entitled "Bone and Regenerative Medicine: Tooth, Bone and Regenerative Medicine"..
  • 2002.11.
Social
Professional and Outreach Activities
2003-: Collaborative research with Sankyo Co.Ltd. on bone metanolism.

2002: Lecture on bone metabolism and regenerative medicine to high school students
of Sainan Gakuin High School, Fukuoka. (Delivery Service of University Lectures programmed by Sainan Gakuin High School)

2001: Collaborative research with Teijin Co.Ltd. (Dr. Ishizuka) on vitamin D antagonists.

2000-: Collaborative research with Kumamoto Flour Milling Company Co.Ltd. on food materials promoting bone health.

1900-1903: Collaborative research with Idemitsu Kosan Co.Ltd. on development of bone metabolism..