In vitro model to optimize mechanical loading to prevent disuse bone atrophy

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671495
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: MORITA Sadao TOKYO MEDICAL AND UNIVERSITY, FACULTY OF MEDICINE, ASSOCIATE PROFESSOR, 医学部附属病院, 助教授 (20202426)
• Co-Investigator(Kenkyū-buntansha): KUMEI Yasuhiro GRADUATE SCHOOL, TOKYO MEDICAL AND UNIVERSITY, ASSISTANT PROFESSOR, 大学院・医歯学総合研究科, 講師 (30161714)
• Project Period (FY): 2001 – 2002
• Keywords: DYSUSE BONE ATROPHY / WEIGHT BEARING / OSTEOBLAST / GRAVITATION / GENE / VITAMIN D

Research Abstract

Disuse syndrome is given much weight in the rehabilitation medicine. Disuse bone atrophy is one of the varied morbidity that is induced by gravity unloading of patients in the long-term bed rest. Eventually, the patients suffer from loss of osseous calcium and bone mass. We have conducted a set of studies in two years. The first experiment was done to analyze the morbidity from the cellular and molecular points in an in vitro simulated model of unloading using rat primary osteoblast cell cultures on a clinostat. We found that gravity unloading suppressed the expression of osteocalcin, a bone-specific matrix protein, and alkaline phosphatase. The second experiment was conducted to analyze the counteracting effects on osteoblasts by hypergravity exposure in a centrifuge. We found for the first time that an appropriate magnitude of gravitational force between 10G and 30G did elevate the expression of osteocalcin and alkaline phosphatase during 24 hours. However, excess gravitational force higher than 30G caused an opposite effects unfavorably and decreased the values of the bone formation markers. At the same time, we clarified that these changes of osteoblastic phenotypic expression were co-related with changes of the transcriptional factors including vitamin D receptor and glucocorticoid receptor. The results suggested that effects of mechanical loading on osteoblasts are observed in the local and systemic factors such as hormone receptors. In summary, we have succeeded in determining the minimum effective magnitude of gravity loading to stimulate bone formation of osteoblasts. Data obtained at the cellular level could be extrapolated to estimating the optimal magnitude of mechanical loading on lower limbs along the longitudinal axis under long-term bed rest The present study indicates the possibility of new medical treatment by controlling the mechanical loading to cure/prevent the patient of disuse bone atrophy.