Exp Clin Endocrinol Diabetes 2006; 114(10): 599-604
DOI: 10.1055/s-2006-924399
Case Report

© J. A. Barth Verlag in Georg Thieme Verlag KG · Stuttgart · New York

Serum Soluble Factors Induce the Proliferation, Alkaline Phosphatase Activity and Transforming Growth Factor-β Signal in Osteoblastic Cells in the Patient with Hepatitis C-associated Osteosclerosis

H. Kaji 1 , J. Naito 1 , H. Sowa 1 , T. Sugimoto 2 , K. Chihara 1
  • 1Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
  • 2Division of Endocrinology, Metabolism and Hematological Oncology, Shimane University School of Medicine, Shimane, Japan
Further Information

Publication History

Received: January 4, 2006 First decision: April 3, 2006

Accepted: May 8, 2006

Publication Date:
19 December 2006 (online)


Hepatitis C-associated osteosclerosis (HCAO) is a rare syndrome characterized by severe, acquired, generalized osteosclerosis and hyperostosis in adults who are infected with the hepatitis C virus. However, the detail of the pathogenesis of HCAO is still unknown. We examined the effects of serum of the HCAO patient on the proliferation, alkaline phosphatase (ALP) activity and transforming growth factor (TGF)-β-Smad signaling in mouse osteoblastic cells. The patient was compatible with HCAO, characterized by high bone mass, bone thickening and bone pain with normal lamelar bone. The serum from the HCAO patient increased the levels of TGF-β and Smad3 expression in osteoblastic MC3T3-E1 cells, compared with the control subject. Moreover, the serum from the HCAO patient significantly augmented TGF-β-induced transcriptional activity with luciferase assay using 3TP-Lux with a Smad3-specific responsive element. In addition, the serum from the HCAO patient significantly stimulated the MTT intensity, the level of proliferating cell nuclear antigen expression, a proliferation marker, and ALP activity in MC3T3-E1 cells, compared with that from the control subject. In conclusion, the present study indicated that the serum from the HCAO patient stimulated TGF-β-Smad signaling, as well as the proliferation and ALP activity in osteoblastic cells. Some soluble factors other than parathyroid hormone might be related to the pathogenesis of HCAO.



Dr. Hiroshi Kaji

Division of Endocrinology/Metabolism

Neurology and Hematology/Oncology

Department of Clinical Molecular Medicine

Kobe University Graduate School of Medicine

7-5-2 Kusunoki-cho


Kobe 650-0017


Email: hiroshik@med.kobe-u.ac.jp