- Title Information
- Title
- Role of SHP2 in Cartilage Anabolism: An In Vitro 3D Culture Studies
- Type of Resource (primo)
- dissertations
- Name:
Personal
- Name Part
- Chonweerawong, Adinai
- Role
- Role Term:
Text
- creator
- Name:
Personal
- Name Part
- Jackson, Cynthia
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Horrigan, Diana
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Yang, Wentian
- Role
- Role Term:
Text
- Advisor
- Name:
Corporate
- Name Part
- Brown University. Biology and Medicine: Biotechnology
- Role
- Role Term:
Text
- sponsor
- Origin Information
- Copyright Date
- 2025
- Physical Description
- Extent
- vii, 42 p.
- digitalOrigin
- born digital
- Note:
thesis
- Thesis (Sc. M.)--Brown University, 2025
- Genre (aat)
- theses
- Abstract
- Abstract of Role of SHP2 in Cartilage Anabolism: An In Vitro 3D Culture Studies, by Adinai Chonweerawong, ScM, Brown University, May 2025
Articular cartilage (AC) is prone to wear and tear, and its ability to regenerate decreases with age due to a lack of chondroprogenitor cells and limited nutrient supply. Efforts to expand chondrocytes in monolayer cultures have been hindered by high rates of dedifferentiation, which results in the loss of key ECM chondrogenic markers such as ACAN, COL2A1, and SOX9. Although the use of 3D chondrocytes culture to address this issue has been reported, most studies have focused on highly proliferative and differentiation-capable cells, such as mesenchymal stem cells (MSCs). This study aims to investigate the AC phenotypic maintenance with a novel 3D culture approach facilitated by SHP2 degradation using the cutting-edge Proteolysis Targeted Chimera (PROTAC) drug SHP2D26. The goal is to better preserve and maintain AC phenotypes by suppressing chondrocyte hypertrophic differentiation and promoting chondrocyte anabolism. My data demonstrate that SHP2D26 treatment of Acan+ AC chondrocytes under 3D culture conditions promote spheroid formation and significantly increases the abundance of SOX9 and SOX9-responsive anabolic gene expression in a time-, concentration-, and context-dependent manner. The importance of SHP2 regulation of SOX9 and SOX9-responsive gene expression is further validated through genetic ablation of SHP2 and SOX9 in Acan+ AC cells using the Crerecombinase system. SHP2 degradation was found to promote AC chondrocyte anabolism in vitro, a phenotype that was correspondingly recapitulated in vivo. These findings suggest that modulating SHP2 expression using the PROTAC SHP2D26 drug in vitro and in vivo may provide a promising platform for articular cartilage anti-degeneration and regeneration.
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01048766")
- Topic
- Osteoarthritis
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01048565")
- Topic
- Orthopedics
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01200078")
- Topic
- Stem cells--Transplantation
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/00858483")
- Topic
- Chondrogenesis
- Subject
- Topic
- 3D Cell Culture
- Language
- Language Term (ISO639-2B)
- English
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20250707