Analysis on the regulatory mechanism of sclerostin expression coupled with RANKL-reverse signaling

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670632
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: IKEBUCHI Yuki 東京大学, 医学部附属病院, 助教 (20645725)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 骨細胞 / 骨代謝カップリング

Outline of Final Research Achievements

Regulatory mechanisms of SOST expression, which is a secreted protein from osteocytes and suppresses bone formation, still remain unclear. We focused on "RANKL reverse signaling" based on RANKL function as a receptor for RANK. At first, we established optimized in vitro assay methods for evaluating osteocyte functions. During 3-dimensional culture composed of type-I collagen and matrigel, osteocytes kept the characteristic features of gene expression and its cell shape over 7 days. Using this novel culture conditions, we examined the effect of RANKL reverse signaling on SOST expression in osteocytes. As a result, activating RANKL reverse signaling resulted in the significant elevation of SOST expression, as well as the ratio of RANKL to OPG expression. Moreover, these effects were also confirmed in mouse in vivo model. Consequently, RANKL reverse signaling in osteocytes may contribute to the efficient bone coupling between bone resorption and formation.

Free Research Field

骨代謝