Investigating Female Predisposition to Musculoskeletal Disease Through In Vitro Spheroid Models of Meniscal Fibrocartilage

Voiceover

Presenter(s)

Alyssa Morrell

Abstract or Description

Osteoarthritis (OA) affects over 300 million people worldwide. The meniscus aids in maintaining knee joint health and, when injured, cannot fully repair itself which often disrupts its function and contributes to OA. Studies show women have higher rates of meniscal injury and follow up repair treatments. Current treatments to counteract an injured meniscus are a partial or total meniscectomy where part or all the meniscus is removed, respectively. This results in aberrant load on the hyaline cartilage and often leads to higher rates of OA. Therefore, it is critical to develop regenerative therapies for meniscus repair. The main markers of regeneration in the meniscus are type I collagen (col 1), type II collagen (col 2), and glycosaminoglycan (GAG). 3D spheroid cultures in vitro were used to mimic the meniscal cell microenvironment and were dosed with transforming growth factor beta-3 (TGFβ-3), a potent transcription factor in meniscus tissue repair that has been shown to increase production of collagen and GAG6. Histology qualitatively assessed cell morphology, organization, and matrix production in spheroids via Hematoxylin and Eosin and Alcian Blue staining. To quantify results, the biochemical assays Dimethyl Methylene Blue and Hydroxyproline examined total GAG and collagen production in response to TGFβ-3. To better understand OA’s sexual dimorphism, male and female donors were compared. The data collected from this study will provide understanding of sex differences in response to known transcription factors and can be used as a platform system to test other biomolecules of interest in meniscus repair and regeneration.

Mentor

Jenny Robinson