Journal of Bone and Mineral Metabolism

, Volume 30, Issue 3, pp 293–303 | Cite as

Overexpression of receptor for hyaluronan-mediated motility (RHAMM) in MC3T3-E1 cells induces proliferation and differentiation through phosphorylation of ERK1/2

  • Hiroko Hatano
  • Hideo Shigeishi
  • Yasusei Kudo
  • Koichiro Higashikawa
  • Kei Tobiume
  • Takashi Takata
  • Nobuyuki Kamata
Original Article


Receptor for hyaluronan (HA)-mediated motility (RHAMM) was first described as a soluble HA binding protein released by sub-confluent migrating cells. We previously found that RHAMM was highly expressed and plays an important role in proliferation in the human cementifying fibroma (HCF) cell line, which we previously established. HCF is a benign fibro-osseous neoplasm of the jaw and is composed of fibrous tissue containing varying amounts of mineralized material. However, the pathogenesis of HCF is not clear. In this paper, we examined the roles of RHAMM in osteoblastic cells. We generated RHAMM-overexpressing MC3T3-E1 cells and examined the cell proliferation and differentiation of osteoblastic cells. In MC3T3-E1 cells, overexpressing RHAMM was located intracellular and activated ERK1/2. Interestingly, the ERK1/2 activated by RHAMM overexpression promoted cell proliferation and suppressed the differentiation of osteoblastic cells. Our findings strongly suggest that RHAMM may play a key role in the osteoblastic differentiation process. The rupture of balance from differentiation to proliferation induced by RHAMM overexpression may link to the pathogenesis of bone neoplasms such as HCF.


Cementifying fibroma RHAMM HA ERK Proliferation 



Receptor for hyaluronan-mediated motility


Extracellular regulated kinase




Mitogen activated protein kinase



This work was supported by a Grant-in-Aid for JSPS fellows (No. 22-6035) from the Japan Society for the Promotion of Science (JSPS).

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

774_2011_318_MOESM1_ESM.pptx (84 kb)
Supplementary material 1 (PPTX 84 kb)


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Copyright information

© The Japanese Society for Bone and Mineral Research and Springer 2011

Authors and Affiliations

  • Hiroko Hatano
    • 1
  • Hideo Shigeishi
    • 1
  • Yasusei Kudo
    • 2
  • Koichiro Higashikawa
    • 1
  • Kei Tobiume
    • 1
  • Takashi Takata
    • 2
  • Nobuyuki Kamata
    • 1
  1. 1.Department of Oral and Maxillofacial Surgery, Division of Cervico-Gnathostomatology, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Department of Oral and Maxillofacial Pathobiology, Division of Frontier Medical Science, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan

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