Research
Osteoarthritis (OA) is the most prevalent degenerative disease in the aging population. Its prevalence and incidence rise rapidly after age 50 and level off after age 70. Humans are unable to repair joint-associated injuries effectively, leading to joint degeneration and OA development, particularly in aging individuals. This underscores a critical unmet need for therapeutic strategies to enhance resilience in OA patients.
In previous work, Hsueh Lab used mass spectrometry-based proteomics to demonstrate robust anabolic effects in human cartilage, especially under the stress of OA (Hsueh et al., Science Advances, 2019). These findings suggest the presence of an endogenous, pro-anabolic mechanism in human joints that could be harnessed to repair injured joint tissue.
Synovial fibroblasts, identified as the most abundant cell type within the synovium from Hsueh Lab鈥檚 previous work, play a crucial role in joint inflammation and tissue remodeling in arthritis. These fibroblasts maintain joint-specific identities and coordinate local cellular environments, highlighting their potential influence on the anabolic mechanisms previously identified in cartilage. This raises the possibility that cartilage anabolic signals may originate from the synovium. To advance therapeutic strategies for OA, particularly in aging populations, Hsueh Lab focuses on defining how aging affects the molecular mechanisms underlying tissue repair and anabolic responses in the joint environment.
The overarching goal of Hsueh Lab is to develop therapies that enhance resilience to OA in aging populations. The current research aims to uncover how aging impacts the body’s endogenous repair mechanisms, with the ultimate objective of reducing OA-associated disability and improving quality of life for older adults.
Building on findings from prior and ongoing studies, Hsueh Lab hypothesizes that aging alters molecular signaling pathways that support joint tissue regeneration.
To address this hypothesis, current research efforts are focused on the following specific aims:
- Investigate the impact of aging on molecular signaling networks in human joint tissues.
- Characterize the functional changes in key regenerative pathways in aging and OA joints.
- Utilize in vivo OA models to elucidate how aging influences the joint’s regenerative capacity and identify potential therapeutic strategies.
These research directions aim to provide critical insights into the interplay between aging, molecular signaling, and joint tissue repair, forming the foundation for innovative OA therapies tailored to the aging population.