Role of estrogen and mechanobiology on meniscal regeneration

这项工作的长期目标是确定雌激素的作用和机制。 微环境对半月板健康和再生的影响，以减少骨关节炎的发作和进展。膝 骨关节炎是导致全球残疾的主要原因， 病人半月板撕裂是最常见的膝关节内损伤， 发展OA。最近的研究表明，成年男性的眼泪更复杂， 与雌性相比，修复率降低，这表明性激素，包括雌激素， 有保护包皮不受撕裂和促进修复的作用。然而，雌激素和 机械环境对区域转录变化、细胞表型和机械转导的影响 尚未确定。因此，本提案旨在通过评估 雌激素处理和基质模量对2D和3D椎间盘纤维软骨细胞影响。的 假设生理雌激素处理和底物模数将促进雌激素水平增加， 细胞外基质的产生和再生将在以下目标中进行研究： 1)阐明雌激素通过雌激素受体α对椎间盘纤维软骨细胞增殖的作用， 细胞外基质产生 2)确定基质模量对纤维软骨细胞迁移、机械转导和 2D和3D中存在雌激素时的表型 破解雌激素促进椎间盘纤维软骨稳态的机制是至关重要的第一步 患者特异性修复和再生的步骤，以减少骨关节炎的进展并缓解 相应的疼痛和不适。

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.