Bone-Targeted Delivery of TGF-Beta Receptor Inhibitor as a Novel Treatment for Osteoarthritis
Abstract
Extreme physical demands contribute to the high incidence of osteoarthritis (OA) in the military population. OA is the most common degenerative joint disorder and the leading cause of physical disability. There is no effective disease-modifying treatment for OA except joint replacement surgery. Additionally, we are lacking fundamental treatment of OA pain although pain is the most prominent symptom of OA and the common reason that military personnel are discharged from service. The prognosis with only analgesia is not satisfactory as it may adversely contribute to the progression of the disease when the primary perception of the joint pathology is blunted. Therefore, there is a tremendous need to develop new therapies to attenuate OA degeneration and alleviate OA pain, thereby improving the quality of life of military soldiers. It has recently been revealed that excessive activation of TGFbeta1 leads to aberrant subchondral bone remodeling and contributes to the onset of joint articular cartilage degeneration. Restoring the structural integrity and mechanical property of the subchondral bone by inhibiting TGFbeta activity was effective in preventing OA progression and cartilage degeneration in OA animal models. However, TGFbetas are multifunctional cytokines that are involved in a range of biological processes. There are significant concerns that systemic inhibition of TGFbeta signaling may lead to a failure in the maintenance of tissue homeostasis of other organs, particularly articular cartilage, where TGFbeta serves as a major anabolic factor. Thus, it is of great importance to develop a novel strategy that can retain the efficacy of the TGFbeta inhibitor while improving its safety in the therapeutic applications. On another aspect, we have found that abnormally elevated osteoclastogenesis substantially contributes to OA pain.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2020
- Accession Number
- AD1110773
Entities
People
- Gehua Zhen