The MC1R Pathway: A Potential Treatment of Osteoarthritis
Molloy Faculty Mentor
Jodi Evans
Presenter Major
Biology Pre-med
Presentation Type
Poster
Location
H239, 2nd floor, Barbara H. Hagan Center for Nursing
Start Date
28-4-2025 5:55 PM
End Date
28-4-2025 6:55 PM
Description (Abstract)
Osteoarthritis (OA) is characterized by articular cartilage degradation in the synovial joints. Over 525 million people around the world suffer from this disease and the most common solution is surgical. A less invasive procedure to treat OA is highly desired. We sought to investigate a potential non-invasive treatment for OA. Previous studies have shown that the melanocortin 1 receptor (MC1R) has protective qualities and reduces the degradation of cartilage. The NDP melanocyte-stimulating hormone (NDP-MSH) is a stable agonist of MC1-R. When MC1-R is activated by its agonist, it has restoration and anti-inflammatory properties in cartilage. We hypothesized that the interaction between NDP-MSH and MC1R should help decrease inflammation and in turn, decrease the degradation of cartilage. Mouse bone marrow-derived mesenchymal stem cells were grown in 2D and 3D cultures and exposed to NDP-MSH. Gene expression of early differentiation markers in the 2D cultures were analyzed using a PCR array to determine effects of MC1-R activation on early chondrogenic development. To examine the impact of MC1-R activation in mature chondrocytes, the 3D cones were differentiated and exposed to NDP-MSH. RNA was isolated from some 3D cultures and others were embedded in paraffin, sectioned, and stained with Masson’s trichrome. Reverse transcription PCR was used to measure gene expression specific chondrogenic markers. The PCR array of 2D cultures revealed NDP-MSH down-regulates inflammatory genes such as Tnf-ɑ. ZFP42 and Pouf5.1, genes that prohibit differentiation, were also down regulated. In the 3D cultures, Acan1, Col2a1, and Mmp13 genes were upregulated, while Adamts4.1 and Adamts5.1 were not. Histologically, there was a trend toward higher cellularity in the NDP-MSH 3D cultures. These data point to increased matrix turnover and not degradation, as a result of MC1R activation. Overall, activation of the
MC1R pathway leads to cartilage growth and turnover while maintaining an anti-inflammatory profile. Agonism of this pathway represents a potential therapeutic in the treatment of OA.
Keywords
osteoarthritis
Related Pillar(s)
Community, Service, Study
The MC1R Pathway: A Potential Treatment of Osteoarthritis
H239, 2nd floor, Barbara H. Hagan Center for Nursing
Osteoarthritis (OA) is characterized by articular cartilage degradation in the synovial joints. Over 525 million people around the world suffer from this disease and the most common solution is surgical. A less invasive procedure to treat OA is highly desired. We sought to investigate a potential non-invasive treatment for OA. Previous studies have shown that the melanocortin 1 receptor (MC1R) has protective qualities and reduces the degradation of cartilage. The NDP melanocyte-stimulating hormone (NDP-MSH) is a stable agonist of MC1-R. When MC1-R is activated by its agonist, it has restoration and anti-inflammatory properties in cartilage. We hypothesized that the interaction between NDP-MSH and MC1R should help decrease inflammation and in turn, decrease the degradation of cartilage. Mouse bone marrow-derived mesenchymal stem cells were grown in 2D and 3D cultures and exposed to NDP-MSH. Gene expression of early differentiation markers in the 2D cultures were analyzed using a PCR array to determine effects of MC1-R activation on early chondrogenic development. To examine the impact of MC1-R activation in mature chondrocytes, the 3D cones were differentiated and exposed to NDP-MSH. RNA was isolated from some 3D cultures and others were embedded in paraffin, sectioned, and stained with Masson’s trichrome. Reverse transcription PCR was used to measure gene expression specific chondrogenic markers. The PCR array of 2D cultures revealed NDP-MSH down-regulates inflammatory genes such as Tnf-ɑ. ZFP42 and Pouf5.1, genes that prohibit differentiation, were also down regulated. In the 3D cultures, Acan1, Col2a1, and Mmp13 genes were upregulated, while Adamts4.1 and Adamts5.1 were not. Histologically, there was a trend toward higher cellularity in the NDP-MSH 3D cultures. These data point to increased matrix turnover and not degradation, as a result of MC1R activation. Overall, activation of the
MC1R pathway leads to cartilage growth and turnover while maintaining an anti-inflammatory profile. Agonism of this pathway represents a potential therapeutic in the treatment of OA.
