Marie Curie research training project on Osteoarthritis

Peptide-based drugs for the treatment of Osteoarthritis!

Maastricht University
Abdullah Khalid

Bid Farewell to Knee Pain: Unlock relief with Innovative Peptide Therapy
Osteoarthritis (OA) is a degenerative joint disease characterized by the progressive breakdown of articular cartilage, leading to joint pain, stiffness, and impaired mobility. It is one of the most prevalent chronic conditions worldwide, affecting millions of people and imposing a significant socioeconomic burden. Despite its high prevalence, there is currently no approved disease-modifying treatment for OA, and existing therapies primarily focus on symptom management1.

Unraveling the inflammatory maze: the molecular criminal in OA
Osteoarthritis (OA) was traditionally seen as a purely degenerative disease, but recent research has shed light on the significant role of inflammation in its pathogenesis. The inflammatory process in OA involves a complex interplay of various molecular pathways and mediators that contribute to cartilage degradation, synovial inflammation, pain and joint tissue destruction2.
The nuclear factor-kappa B (NF-κB) pathway is a central regulator of inflammation in OA. It mediates the expression of various inflammatory genes, including those encoding cytokines (e.g., IL-1β, TNF-α, IL-6), chemokines (e.g., IL-8, CCL2), and matrix-degrading enzymes (e.g., MMPs, ADAMTS). Activation of the NF-κB pathway in chondrocytes and synovial cells perpetuates the inflammatory cascade, leading to cartilage degradation and synovial inflammation5.
Various inflammatory mediators, including cytokines (e.g., IL-1β, TNF-α, IL-6), chemokines (e.g., IL-8, CCL2), and matrix-degrading enzymes (e.g., MMPs, ADAMTS), play crucial roles in the inflammatory process of OA. These mediators are produced by chondrocytes, synovial cells, and infiltrating immune cells, contributing to cartilage degradation, synovial inflammation, and joint tissue destruction2,3,4.

Anti-inflammatory peptide: The criminal justice
What if I tell you that we can design a peptide derived from a key component of the NF-κB pathway and it reduces inflammation? Sounds cool, right? At the Molecular Cartilage Biology group at the Department of Orthopedic Surgery at Maastricht University (NL) we are working on designing anti-inflammatory peptides. Since p65 is an essential protein subunit (transcription factor) that binds to the DNA to promote the expression of inflammatory genes, it is therefore a potential target to be blocked to inhibit the inflammation. Based on the amino-acid sequence of p65, a bioactive peptide was synthesized (“anti-p65 peptide”) that can bind to other NF-κB subunits preventing nuclear translocation of the complex and thereby preventing NF-κB/p65 related inflammatory signaling. This anti-p65 peptide was then coupled to different peptide sequences that can facilitate penetration of the anti-p65 peptide into the cell6.


The development of an innovative anti-inflammatory peptide therapy by researchers at Maastricht University may represent a promising breakthrough in the treatment of osteoarthritis (OA). By targeting the NF-κB pathway, a central regulator of inflammation in OA, this novel peptide therapy offers a targeted and potentially safer approach to address one of the root causes of the disease.
The anti-p65 peptide may have the potential to alleviate inflammation, reduce cartilage degradation, and mitigate joint tissue destruction – the hallmarks of OA pathogenesis. Furthermore, the successful coupling of the anti-p65 peptide with cell-penetrating sequences enhances its therapeutic potential, ensuring efficient delivery and bioavailability within the target cells.
This groundbreaking peptide therapy represents a beacon of hope for millions of individuals suffering from OA worldwide, offering a safe and effective solution to alleviate the burden of this chronic condition and improve the quality of life for those affected. With continued research and future clinical trials, this innovative therapeutic strategy may become a reality, bidding farewell to the debilitating effects of knee pain and ushering in a new era of personalized and precision medicine in the management of OA.

Future Prospects:

Our team at OSTASKILLS is dedicated to advancing peptide-based therapeutics for the management of osteoarthritis (OA), with a focus on developing a disease-modifying treatment for patients suffering from OA. Through rigorous in vitro and pre-clinical studies evaluating the efficacy and safety of our peptide drug candidate, we aim to bridge the treatment gap and provide innovative solutions to address the existing unmet need for effective OA therapies. Our approach involves conducting comprehensive pre-clinical tests to validate the potential of our peptide-based therapy to modify the disease course and alleviate symptoms associated with knee OA.


1. Goldring, M. B., & Otero, M. (2011). Inflammation in osteoarthritis. Current opinion in rheumatology, 23(5), 471-478.
2. Vilá, S. (2017). Inflammation in osteoarthritis. Puerto Rico health sciences journal, 36(3), 123-129.
3. Greene, M. A., & Loeser, R. F. (2015). Aging-related inflammation in osteoarthritis. Osteoarthritis and cartilage, 23(11), 1966-1971.
4. Berenbaum, F. (2013). Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis and cartilage, 21(1), 16-21.
5. Chow, Y. Y., & Chin, K. Y. (2020). The role of inflammation in the pathogenesis of osteoarthritis. Mediators of inflammation, 2020.
6. Takada, Y., Singh, S., & Aggarwal, B. B. (2004). Identification of a p65 peptide that selectively inhibits NF-κ B activation induced by various inflammatory stimuli and its role in down-regulation of NF-κB-mediated gene expression and up-regulation of apoptosis. Journal of Biological Chemistry, 279(15), 15096-15104.