Role of estrogen and mechanobiology on meniscal regeneration

雌激素和力学生物学对半月板再生的作用

• 批准号: 10203229
• 负责人: Jennifer Lindsey Robinson
• 金额: $ 18.67万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10203229
• 关键词: Role; estrogen; mechanobiology; meniscal; regeneration

The long-term objective of the proposed work is to determine the role of estrogen and the mechanical microenvironment on meniscus health and regeneration to reduce osteoarthritis onset and progression. Knee osteoarthritis is a major cause of global disability resulting in over $6,000 in annual healthcare costs per patient. Meniscal tears are the most prevalent intra-articular knee injury and pose significant risk in the development of OA. Recent studies have shown that adult males experience greater tear complexity and have a reduced repair rate compared to females suggesting that sex hormones, including estrogen, may play a role in protecting the menisci from tear and promote repair. However, the differential role of estrogen and the mechanical environment on regional transcriptional changes, cell phenotype, and mechanotransduction have not been determined. Thus, this proposal aims to tackle this overarching question by evaluating the effect of estrogen treatment and substrate modulus on meniscal fibrochondrocytes in 2D and 3D. The hypothesis that physiological estrogen treatment and substrate modulus will promote an increase in meniscal extracellular matrix production and regeneration will be investigated in the following aims: 1) Elucidate the role of estrogen via estrogen receptor alpha on meniscal fibrochondrocyte proliferation and extracellular matrix production 2) Determine impact of substrate modulus on fibrochondrocyte migration, mechanotransduction, and phenotype in the presence of estrogen in 2D and 3D Deciphering the mechanism by which estrogen promotes meniscal fibrocartilage homeostasis is a vital first step in patient-specific repair and regeneration to reduce osteoarthritis progression and alleviate the corresponding pain and discomfort.

本研究的长期目标是确定雌激素和机械的作用