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Thomas Jefferson University - Motomi Enomoto-Iwamoto, Ph.D, D.D.S
Motomi Enomoto-Iwamoto, Ph.D, D.D.S

Orthopaedic Surgery
Thomas Jefferson University
Jefferson Medical College
Department of Orthopaedic Surgery
Associated Professor
Appointed: 2002
Mailing Address
1015 Walnut street, Curtis 501
Philadelphia, Pennsylvania 19107
United States
Contact Information
Motomi.Iwamoto@jefferson.edu
Qualifications
D.D.S, Osaka University, 1983

Ph.D., Osaka University, Biochemistry, 1987
Expertise and Research Interests
My research interests are to determine the regulatory mechanism of cartilage development, especially endochondral ossification and to understand pathogenesis of joint diseases such as osteoarthritis. Recently we are focusing on Wnt signaling, which exerts critical roles in a variety of biological processes. We have demonstrated that a major Wnt pathway, beta-catenin-LEF/TCF dependent signaling is essential for progression of chondrocyte maturation during skeletal formation. Now we are investigating 1) how this signaling regulates cartilage matrix turn-over and its replacement to bone, 2) how this signaling interacts with other important pathways including retionid and BMP signaling and 3) whether this signaling is involved in pathological degeneration of articular cartilage in joints. We are also interesting in regulation of cytoskeletal structures of chondrocytes. We have found that Rac-1, a small GTPase protein plays important roles in regulation of cell shape and function in chondrocytes. We are now studying on upstream and downstream of Rac-1 proteins.
Keywords
Cartilage; chondrocyte; Wnt; beta-catenin; endochondral ossification; osteoarthritis; small GTPase
Publications
  • 1. I. Matsui, S. Otani, S. Morisawa, M. Takigawa, M. Enomoto and F. Suzuki (1985) Induction of ornithine decarboxylase and spermidine/spermine N1-acetyltransferase by parathyroid hormone in rabbit costal chondrocytes in culture. J. Biochem.(Tokyo), 97, 387-390.

  • 2. M. Takigawa, E. Shirai, M. Enomoto, Y. Hiraki, M. Fukuya, F. Suzuki, T. Shiio and Y. Yugari (1985) Cartilage-derived anti-tumor factor (CATF) inhibits the proliferation of endothelial cells in culture. (1985) Cell Biol. Int. Rep., 9, 619-625.

  • 3. M. Takigawa, M. Takano, K. Fukuo, E. Shirai, M. Enomoto and F. Suzuki (1985) The role of polyamines in the restoration of the differentiated phenotypes of chondrocytes from de-differentiated cells pretreated with retinoic acid and a tumor promoter. In "Polyamines Basic and Clinical Aspects", VNU Science Press, The Netherlands.

  • 4. K. Fukuo, M. Takigawa, K. Tajima, M. Enomoto, Y. Kumahara and F. SuzukiComparison of inhibition by a tumor promoter (12-O-tetradecanoylphorbol-13-acetate) of expression of the differentiated phenotype of chondrocytes in rabbit costal chondrocytes in culture with inhibition by retinoic acid., J. Biochem.(Tokyo) (1986) 99, 385-396.

  • 5. M. Takigawa, E. Shirai, M. Enomoto, H.-O. Pan, F. Suzuki, T. Shiio and Y. Yugari A factor in conditioned medium of rabbit costal chondrocyte inhibits the proliferation of cultured endothelial cells and angiogenesis induced by B16 melanoma: Its relation with cartilage-derived anti-tumor factor (CATF)., Biochem. Int., (1987) 14, 357-363.

  • 6. M. Takigawa, M. Enomoto, E. Shirai, Y. Nishii and F. Suzuki. Differential effects of 1a, 25-dihydroxycholecalciferol on the proliferation and the differentiated phenotype of rabbit costal chondrocytes in culture. Endocrinology, (1988) 122,831-839.

  • 7. M. Takigawa, E. Shirai, M. Enomoto, Y. Hiraki, F. Suzuki, T. Shiio and Y. Yugari Cartilage-derived anti-tumor factor (CATF): Partial purification and correlation of inhibitory activity against tumor growth with anti-angiogenic activity., J. Bone Mineral. Metab. (1988) 6, 83-92.

  • 8. M. Takigawa, E. Shirai, M. Enomoto, A. Kinoshita, H.-O. Pan, F. Suzuki and Y. Yugari. Establishment from mouse growth cartilage of clonal cell lines with osteoblastic phenotypes and ability to produce an endothelial cell growth inhibitor., Calcified. Tissue Int. (1989) 45, 305-313.

  • 9. M. Enomoto, A. Kinoshita, H.-O. Pan, F. Suzuki, I. Yamamoto and M. Takigawa Demonstration of receptors for parathyroid hormone on cultured rabbit costal chondrocytes., Biochem. Biophys. Res. Commun. (1989)162, 1222-1229.

  • 10. M. Takigawa, K. Tajima, H.-O. Pan, M. Enomoto, A. Kinoshita, F. Suzuki, Y. Takano and Y. Mori. Establishment of a clonal human chondrosarcoma cell line with cartilage phenotypes., Cancer Res. (1989) 49, 3996-4002.

  • 11. M. Enomoto, H.-O. Pan, F. Suzuki and M. Takigawa. Physiological role of vitamin A in growth cartilage cells: Low concentrations of retinoic acid strongly promote the proliferation of rabbit costal growth cartilage cells in culture., J. Biochem. (Tokyo), (1990) 107, 743-748

  • 12. M. Enomoto, H.-O. Pan, A. Kinoshita, Y. Yutani, F. Suzuki and M. Takigawa Effects of tumor necrosis factor on proliferation and expression of differentiated phenotypes in rabbit costal chondrocytes in culture. Calcif.Tissue Int. (1990) 47,145-151.

  • 13. M. Takigawa, H.-O. Pan, M. Enomoto, A. Kinoshita, Y. Nishida, F. Suzuki and K. Tajima. A clonal human chondrosarcoma cell line produces an anti-angiogenic antitumor factor. Anticancer Res. (1990) 10, 311-316.

  • 14. M. Takigawa, M. Enomoto, Y. Nishida, H.-O. Pan, A. Kinoshita and F. Suzuki Tumor angiogenesis and polyamines: a-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, inhibits B16 melanoma-induced angiogenesis in ovo and the proliferation of vascular endothelial cells in vitro. Cancer Res. (1990) 50, 4131-4138.

  • 15. M. Takigawa, A. Kinoshita, M. Enomoto, A. Asada and F. Suzuki. Effects of various growth and differentiation factors on expression of parathyroid hormone receptors on rabbit chondrocytes in culture. Endocrinology (1991)129, 868-876.

  • 16. P. S. Leboy, A. S. Menko, D. Beottiger and M. Enomoto. Ascorbic acid induction of chondrocyte maturation. Bone and Mineral. (1992)17, 242-246.

  • 17. M. Enomoto, D. Boettiger and A.S. Menko. a5 integrin is a critical component of adhesion plaques in myogenesis., Dev. Biol. (1993)155, 180-197.

  • 18. M. Enomoto, P.S. Leboy, A.S. Menko and D. Boettiger. b1 integrins mediate the interaction with type I collagen, type II collagen and fibronectin in chondrocytes., Exp. Cell Res. (1993) 205, 276-285.

  • 19. M. Enomoto-Iwamoto, A.S. Menko, N. Philp and D. Boettiger. Evaluation of integrin molecules involved in substrate adhesion.Cell Adhesion and Commun. (1993)1,191-202.

  • 20. M. Iwamoto, A. Jikko, H. Murakami, A. Shimazu, K. Nakashima, M. Iwamoto, M. Takigawa, H. Baba, F. Suzuki and Y. Kato. Changes in parathyroid hormone receptors during chondrocyte cytodifferentiation., J. Biol. Chem. (1994) 289, 1-7.

  • 21. T. Takebayashi, M. Iwamoto, A. Jikko, T. Matsumura, M. Enomoto-Iwamoto, F. Myoukai, E. Koyama, T. Yamaai, K. Matsumoto, T. Nakamura, K. Kurisu and S. Noji Hepatocyte growth factor/scatter factor modulates cell motility, proliferation, and proteoglycan synthesis of chondrocytes. J. Cell Biol. (1995) 129, 1411-1419

  • 22. D. Boettiger, M. Enomoto-Iwamoto, H. Yoon, U. Hofer, A. S. Menko and R. Chiquet-Ehrismann, Regulation of a5b1 integrin affinity during myogenic differentiation. Dev. Biol. (1995)169, 261-272

  • 23. Y. Kawakami, T. Ishikawa, M. Shimbara, N. Tanda, M. Enomoto-Iwamoto, M. Iwamoto, T. Kuwana, S. Noji and T. Nohno, BMP signaling during bone pattern determination in the developing limb. Development (1996)122, 3557-3566

  • 24. N. Kinto, M. Iwamoto, M. Enomoto-Iwamoto, S. Noji, H. Ohuchi, H. Yoshioka, H. Kataoka, Y. Wada, G. Yuhao, H. E. Takahashi, S. Yoshiki and A. Yamaguchi, Fibroblasts expression Sonic hedgehog induce osteoblast differentiation and ectopic bone formation. FEBS Lett. (1997) 404, 319-323

  • 25. M. Enomoto-Iwamoto, M. Iwamoto, K. Nakashima, Y. Mukudai, D. Boettiger, M.Pacifici, K. Kurisu and F. Suzuki, Involvement of a5b1 integrin in matrix interactions and proliferation of chondrocytes. J. Bone Miner. Res. (1997)12, 1124-1132

  • 26. T. Nakamura, T. Aikawa, M. Enomoto-Iwamoto, M. Iwamoto, Y. Higuchi, M. Pacifici, N. Kinto, A. Yamaguchi, S. Noji, K. Kurisu and T. Matsuya, Induction of osteogenic differentiation by hedgehog proteins. Biochem. Biophys. Res. Commun. (1997) 237, 465-469

  • 27. M. Enomoto-Iwamoto, M. Iwamoto, Y. Mukudai, Y. Kawakami, T. Nohno, Y. Higuchi, S. Takemoto, H. Ohuchi, S. Noji and K. Kurisu, Bone Morphogenetic Protein Signaling Is Required for Maintenance of Differentiated Phenotype, Control of Proliferation and Hypertrophy in Chondrocytes. J.Cell Biol. (1998)140, 409-418

  • 28. A. Jikko, K. Yamashita, M. Iwamoto, H. Hiranuma, T. Takebayashi, T. Maeda, M. Sakuda, K. Matusmoto, T. Nakamura, M. Enomoto-Iwamoto, M. J. Tabata, H. Fuchihata, K. Kurisu. The role of hepatocyte growth factor in growth plate cartilage., J. Bone Miner. Metab. (1998) 16, 170-177.

  • 29. K. Imanaka-Yoshida, M. Enomoto-Iwamoto, T. Yoshida and T. Sakakura Vinculin, talin, integrin a6b1 and laminin can serve as components of attachment complex mediating contraction force transmission from cardiomyocytes to extracellular matrix. Cell Motil Cytoskel. (1999) 42, 1-11

  • 30. Enomoto, H., Enomoto-Iwamoto, M., Iwamoto, M., Takemoto, S., Himeno, M., Nomura, S., Kitamura, Y., Kishimoto, T., Komori, T. Cbfa-1 is a positive regulatory factor in chondrocyte maturation. J. Biol. Chem. (2000) 275, 8695-8702

  • 31. Yagami, K.,Suh, J.-Y., Enomoto-Iwamoto, M., Koyama, E., Shapiro, I.M., Pacifici, M., Iwamoto, M. Matrix GLA protein is a developmental regulator of chondrocyte mineralization and, when constitutively expressed, blocks endochondral and intramembranous ossification in the limb. J. Cell Biol. (1999) 147, 1097-1108

  • 32.Iwamoto M, Higuchi Y, Koyama E, Enomoto-Iwamoto M, Kurisu K, Yeh H, Abrams

  • WR, Rosenbloom J, Pacifici M.Transcription factor ERG variants and functional diversification of chondrocytesduring limb long bone development.J Cell Biol. 2000 Jul 10;150(1):27-40.

  • 33. Enomoto-Iwamoto M, Nakamura T, Aikawa T, Higuchi Y, Yuasa T, Yamaguchi A,

  • Nohno T, Noji S, Matsuya T, Kurisu K, Koyama E, Pacifici M, Iwamoto M.Hedgehog proteins stimulate chondrogenic cell differentiation and cartilageformation.J Bone Miner Res. 2000 Sep;15(9):1659-68.

  • 34. Ueta, C., Iwamoto, M., Kanatani, N., Yoshiada, C., Liu, Yang, Enomoto-Iwamoto, M., Ohmori, T., Enomoto, H., Nakata, K., Takada, K., Kurisu, K. and komori, T. Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes. J. Cell Biol. (2001) 153, 87-99.

  • 35. Enomoto-Iwamoto, M., Enomoto, Y., Komori, T., and Iwamoto, M. Participation of cbfa1 in regulation of chondrocyte differentiation. Osterarthritis & Cartilage (2001) 9, S76-S84.

  • 36. Iwamoto, M., Higuchi, Y., Enomoto-Iwamoto, M., Kurisu, K., Koyama, E., Yeh, H., Rosenbloom, J., and Pacifici, M. The role of erg (ets related gene) in cartilage development. Osterarthritis & Cartilage (2001) 9, S41-S47.

  • 37. Enomoto-Iwamoto, M., Kitagaki, J., Koyama, E., Tamamura, Y., Wu, C., Kanatani, N., Koike, T., Okada, H., Komori, T., Yoneda, T., Church, V., Francis-West, P. H., Kurisu, K., Nohno, T., Pacifici, M., and Iwamoto, M. The wnt antagonist Frzb-1 regulates chondrocyte maturation and long bone development during limb skeletogenesis. Dev. Biol. (2002), 251, 142-156.

  • 38. Yuasa T., Kataoka H., kinto N., Iwamoto M., Enomoto-Iwamoto M., Iemura S., Ueno N,m Shibata, Y., Kurosawa H. and Yamaguchi A. Sonic hedgehog id involved in osteoblast differentiation by cooperating with BMP-2. J Cell Physiol. (2002) 193, 225-32.

  • 39. Iwamoto, M. Kitagaki, J., Tamamura, Y., Gentili, C., Koyama, E., Enomoto, H., Komori, T., Pacifici, M., and Enomoto-Iwamoto, M. Runx2 expression and action in chondrocytes are regulated by retinoid signaling and parathyroid hormone-related peptide (PTHrP). Osteoarthritis and Cartilage (2003) 11, 6-15.

  • 40. Kitagaki, J. ,Iwamoto, M., Liu, L.-G., Tamamura, Y., Pacific, M., Enomoto-Iwamoto, M. Activation of beta-catenin-LEF/TCF signal pathway in chondrocytes stimulates ectopic endochondral ossification. Osteoarthritis and Cartilage (2003) 11, 36-43.

  • 41. Enomoto, H., Furuichi, T., Zanma, A., Yamada, K., Yoshida, C., Sumitani, S., Yamamoto, H., Enomoto-Iwamoto, M., Iwamoto, M. and Komori, T. Runx2 deficiency in chondrocytes causes adipogenic changes in vitro. J Cell Sci. (2004) 117, 417-425.

  • 42. Iwamoto, M., Koyama, E., Enomoto-Iwamoto, M., and Pacifici, M. The balancing act of transcription factors C-1-1 and Runx2 in articular cartilage development. Biochem. Biophys. Res. Commun. (2005) 328, 777-782.

  • 43. Tamamura, Y., Otani, T., Kanatani, N., Koyama, E., Kitagaki, J., Komori, T., Yamada, Y., Costantini, F., Wakisaka, S., Pacifici, M., Iwamoto, M. and Enomoto-Iwamoto, M. Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and eodochodnral ossification. J. Biol. Chem. (2005) 280, 19185-95

  • 44. Pacifici M. Koyama E., Shibukawa Y., Wu C,m Tamamura T., Enomoto-Iwamoto M. and Iwamoto M. Cellular and molecular mechanisms of synovial joint and articular cartilage formation. Ann N Y Acad Sci. (2006) 1068, 74-86

  • 45. Young B., Minugh-Purvis N., Shimo T., St-Jacques B., Iwamoto M., Enomoto-Iwamoto M., Koyama E. and Pacifici M. Indican and sonic hedgehogs regulate synchondrosis growth plate and cranial base development and function. Dev. BIol. (2006) 229, 272-82

  • 46. Koyama E., Nagayama M., Shibukawa Y., Enomoto-Iwamoto M., Iwamoto M., Maeda T., Lanske B., Song B., Serra R., Pacifici M. Conditional Kif3a ablation causes abnormal hedgehog signaling topography, growth plate dysfunction, and excessive bone cartilage formation during skeletogenesis. Development (2007) 134, 2159-69

  • 47. Iwamoto M., Tamamura Y., Koyama E., Komori T., Takeshita N., Williams J.A., Nakamura T., Enomoto-Iwamoto M., Pacifici M. Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis. Dev. Biol. (2007) 305, 40-51.

  • 48. Dong Y.F., Soung D. Y., Chang Y., Enommoto-Iwamoto M., Paris M., OKeefe R. J., Schwarz E. M., and Drissi H. TGF-b and Wnt signals stage-sepcifically regulate chondrocyte differentiation through Twist1. Mol Endocrinol, (2007) 21, 2805-20.

  • 49. Koyama E., Oshiai T., Rountree R. B., Kingsley D. M., Enomoto-Iwamoto M., Iwamoto M., and Pacifici M. Synovial joint formation during mouse limb skeletogenesis: Roles of Indian Hedgehog Signaling. Ann N Y Acad Sci (2007) 1116, 100-12.

  • 50. Yuasa T., Otani T., Koike T., Iwamoto M and Enomoto-Iwamoto M. Wnt/beat-catenin signaling stimulates matrix catabolic genes and activity in articular chondrocytes: its possible role in joint degeneration. Lab Invest (2008) in press.

  • 51. Nagayama M., Iwamoto M., Hargett A., Kamiya N., Tamamura Y., Young B., Morrison T., Takeuchi H., Pacifici M., Enomoto-Iwamoto M., Koyama E. Wnt/beta-catenin signaling regulates cranial base development and growth. J Dent Res (2008) in press.

  • 52. Koyama E., Shibukawa Y., Nagayama M., Sugito H., Young B., Yuasa T., Okabe T., Ochiai T., Kamiya N., Rountree R.B., Kingsley D. M., Iwamoto M., Enomoto-Iwamoto M., Pacific M. A distinct cohort of progenitor cells participates in synovial joint and articular cartilage formation during mouse limb skeletogenesis. Dev. Biol (2008) in press.

  • 53. Kerr B.A., Otani T., Koyama E., Freeman T.A., Enomoto-Iwamoto M. Small GTPase protein Rac-1 is activated with maturation and regulates cell morphology and function in chondrcotyes. Exp Cell Res (2008) in press.

Individual Expertise profile of Motomi Enomoto-Iwamoto, Ph.D, D.D.S, Copyright © Motomi Enomoto-Iwamoto, Ph.D, D.D.S.
Last Updated by Motomi Enomoto-Iwamoto, Ph.D, D.D.S : Tuesday, April 15, 2008 2:16:58 PM



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