Search the Potential Mediators/Compounds from the Progression of Loading-Induced Bone Formation for Osteoporosis Treatment

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基本資料

Project title

Code/計畫編號

MOST103-2321-B400-011-MY3

Translated Name/計畫中文名

從機械力撞擊誘導骨骼生成過程中尋找治療骨質疏鬆症的可能調控因子或成份

Project Coordinator/計畫主持人

Ding-Yu Lee

Funding Organization/主管機關

National Science and Technology Council

Department/Unit

Institute of Cellular and System Medicine,National Health Research Institutes

Website

https://www.grb.gov.tw/search/planDetail?id=11263421

Year

2015

Start date/計畫起

01-08-2015

Expected Completion/計畫迄

31-07-2016

Bugetid/研究經費

1000千元

ResearchField/研究領域

基礎醫學
藥學

骨質疏鬆症被認為是影響人類十大重要疾病之一，世界衛生組織將其定義為低骨骼質量及骨組織微結構惡化的骨骼疾病，目前主要治療方向為促進骨骼生長或抑制骨吸收。機械力撞擊 (Mechanical loading)是刺激骨骼生長的重要因子，缺少了此機械力刺激將會導致於骨骼疏鬆。當骨骼接受持續的撞擊，內部的細胞間流 (interstitial fluid flow) 將會引起往複式流體 (reciprocating flow)。文獻指出骨細胞 (osteocyte)及造骨細胞 (osteoblast)是兩種接受此流體刺激的主要細胞，能啟動內部訊息調控骨骼生長。然而此兩種細胞與蝕骨細胞 (osteoclast)三者之間的互動在撞擊刺激骨骼生長過程中的角色仍待釐清。我們之前研究指出往複式流體可以促進造骨細胞內部的骨骼生成及增生訊息。我們推測往複式流體將也可能誘使機械力接受細胞 (mechanosensitive cells)釋放調節因子 (mediators)，影響效用細胞 (effector cells)的功能。因此，本計畫主要目標在於釐清往複式流體及細胞間的溝通影響撞擊刺激骨骼生成之細胞與分子機制。共培養流體系統、蛋白質體學、生化與分生相關尖端技術將被使用於研究此目標，並從中尋找具有促進骨骼生成及抑制骨骼吸收的調控因子，進而使用骨質疏鬆症的動物模式對其療效進行評估。釐清這些可能調控因子或成份對於骨骼生成的功能性，將有助於我們了解撞擊刺激骨骼生長的詳細機制，並將對於骨質疏鬆症的治療及骨組織工程的發展提供新的舞台。 Osteoporosis is identified as one of the 10 most important conditions affecting the entire human race. The World Health Organization (WHO) defines osteoporosis as “a systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture”. The goal of osteoporosis treatment can be achieved either by increasing bone formation or decreasing bone resorption. Mechanical loading is critical for new bone formation. Loss of loading, such as prolonged bed rest, can result in osteoporosis. During dynamic and periodic loading of intact bone, the interstitial fluid flow drives reciprocating flow through the lacuno-canalicular space and across the bone cells, providing nutrients and mechanical stimuli on the bone cell membranes. Recently studies suggested that osteocyte and osteoblast are mechanosensitive bone cells in response to loading-induced interstitial fluid flow, and these cells can turn on their signaling transduction to modulate bone formation. However, the relationship between the bone cells involved in loading-induced bone formation, including osteocyte, osteoblast, and osteoclast, still need to be defined. We previously demonstrated that loading-induced interstitial fluid flow increases bone formation-related signaling and proliferative signaling in osteoblast to promote bone formation. It is proposed that loading-induced interstitial fluid flow exerts mechanical signaling on mechanosensitive cells, including osteocyte and osteoblast, and induces their release of a number of mediators, leading to functional modulation of effector cells to regulate bone remodeling. The aim of this proposal project is to elucidate the molecular and cellular bases for the role of loading-induced reciprocating flow and cell-cell intercommunication in the progression of loading-induced bone formation, in terms of enhancement of proliferative and bone formation-related signaling in osteoblast, up-regulation of osteoblastic factor expression in osteocyte, and respression of osteoclastic activity of osteoclast. A series of comprehensive, state-of-the-art approaches (including proteomic, genomic, biochemical, and molecular biological methods, etc.) will be used to investigate the molecular and cellular basis for the role of loading-induced interstitial fluid flow and cell-cell intercommunication in the progression of bone formation and identify the candidate mediators released by mechanosensitive cells to modulate bone remodeling in our newly co-culture flow system. Furthermore, the therapeutic effect of these potential mediators/compounds on the formation and progression of osteoporosis will be defined by osteoporosis animal model. The elucidation of functional roles of these potential mediators/compounds in bone formation will contribute to our understanding of the detailed mechanism of loading-induced bone formation and the development of new strategies for osteoporosis treatment and bone tissue engineering.

Keyword(s)

骨質疏鬆症
細胞間流
撞擊刺激骨骼生成
來回式流體
細胞間的溝通
骨骼生長
骨吸收
骨細胞
造骨細胞
蝕骨細胞
Osteoporosis
loading-induced bone formation
interstitial fluid flow
reciprocating flow
cell-cell intercommunication
bone formation
bone resorption
osteocyte
osteoblast

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Search the Potential Mediators/Compounds from the Progression of Loading-Induced Bone Formation for Osteoporosis Treatment

基本資料

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