Abstract Title

The Therapeutic Effect of GPNMB/Osteoactivin in a Traumatically Induced Osteoarthritic Mouse Model

Abstract

Osteoarthritis is a severe joint disease that affects millions of people. At this time, the current treatment for osteoarthritis is total joint reconstruction surgery. GPNMB/Osteoactivin plays a key role in bone remodeling and bone growth. Data from our lab suggested that GPNMB/Osteoactivin is positive regulator of osteoblastogenesis and a negative regulator of osteoclastogenesis. Furthermore, the role of GPNMB/Osteoactivin in cartilage has not been investigated before. Treatment of human chondrocytes with GPNMB/Osteoactivin results in a significant increase in collagen Type II and Sox9 expression. In this study, we examined whether recombinant GPNMB/Osteoactivin has an anabolic effect on a model of post-traumatic osteoarthritis. The DMM (destabilization of the medial meniscus) in mice has been found to be an excellent model for studying post-traumatic osteoarthritis . We performed the DMM surgery on 28 C57/BL6 mice. Moderate to severe osteoarthritis develops around six to eight weeks with this model. We will inject pharmaceutical grade recombinant GPNMB/Osteoactivin into the joint capsule of the mice at six weeks. The experiment will be terminated at twelve weeks, and the joints will be collected for microCT analysis and immunohistochemistry. The serum from the blood will be analyzed via Elisa. Based on preliminary studies performed in our lab, we expect cartilage degeneration to be dramatically decreased in response to the therapeutic effects of GPNMB/Osteoactivin. A protective factor against osteoarthritis progression, osteoactivin-injected mice should have remarkably better articular cartilage in comparison to the control group, proving GPNMB/Osteoactivin a promising therapy in lieu of total joint reconstruction.

Modified Abstract

Osteoarthritis is a severe joint disease that affects millions of people. At this time, the current treatment for osteoarthritis is total joint reconstruction surgery. GPNMB/Osteoactivin plays a key role in bone remodeling and bone growth. Data from our lab suggested that GPNMB/Osteoactivin is positive regulator of osteoblastogenesis and a negative regulator of osteoclastogenesis. Furthermore, the role of GPNMB/Osteoactivin in cartilage has not been investigated before. Based on preliminary studies performed in our lab, we expect cartilage degeneration to be dramatically decreased in response to the therapeutic effects of GPNMB/Osteoactivin. A protective factor against osteoarthritis progression, osteoactivin-injected mice should have remarkably better articular cartilage in comparison to the control group, proving GPNMB/Osteoactivin a promising therapy in lieu of total joint reconstruction.

Research Category

Biomedical Sciences

Primary Author's Major

Biology

Mentor #1 Information

Dr. Fayez Safadi

Presentation Format

Oral

Start Date

21-3-2017 1:00 PM

Research Area

Medical Cell Biology | Musculoskeletal Diseases | Musculoskeletal, Neural, and Ocular Physiology | Musculoskeletal System

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Mar 21st, 1:00 PM

The Therapeutic Effect of GPNMB/Osteoactivin in a Traumatically Induced Osteoarthritic Mouse Model

Osteoarthritis is a severe joint disease that affects millions of people. At this time, the current treatment for osteoarthritis is total joint reconstruction surgery. GPNMB/Osteoactivin plays a key role in bone remodeling and bone growth. Data from our lab suggested that GPNMB/Osteoactivin is positive regulator of osteoblastogenesis and a negative regulator of osteoclastogenesis. Furthermore, the role of GPNMB/Osteoactivin in cartilage has not been investigated before. Treatment of human chondrocytes with GPNMB/Osteoactivin results in a significant increase in collagen Type II and Sox9 expression. In this study, we examined whether recombinant GPNMB/Osteoactivin has an anabolic effect on a model of post-traumatic osteoarthritis. The DMM (destabilization of the medial meniscus) in mice has been found to be an excellent model for studying post-traumatic osteoarthritis . We performed the DMM surgery on 28 C57/BL6 mice. Moderate to severe osteoarthritis develops around six to eight weeks with this model. We will inject pharmaceutical grade recombinant GPNMB/Osteoactivin into the joint capsule of the mice at six weeks. The experiment will be terminated at twelve weeks, and the joints will be collected for microCT analysis and immunohistochemistry. The serum from the blood will be analyzed via Elisa. Based on preliminary studies performed in our lab, we expect cartilage degeneration to be dramatically decreased in response to the therapeutic effects of GPNMB/Osteoactivin. A protective factor against osteoarthritis progression, osteoactivin-injected mice should have remarkably better articular cartilage in comparison to the control group, proving GPNMB/Osteoactivin a promising therapy in lieu of total joint reconstruction.