Neogenin, Osteoarthritis, and Osteoporosis

Orthopedics This Week
Elizabeth Hofheinz, M.P.H., M.Ed. • Tue, Aug 10th, 2010
Copyright 2009-2010 RRY Publications

Another step toward cracking the osteoarthritis and osteoporosis codes? Researchers from Medical College of Georgia (MCG) have found that too little of a protein called neogenin results in a smaller skeleton during development and sets the stage for a more fragile bone framework lifelong. The team found that a developing mouse with neogenin deficits has poorly defined digits and is generally smaller, including having small growth plates. Dr. Zheng Zhou, MCG assistant research scientist, is first author. Dr. Wen-Cheng Xiong, developmental neurobiologist in the MCG Schools of Medicine and Graduate Studies, is a corresponding author of the study.

“Each cell type has a master gene. Neogenin is not that, it’s more of a modulator,” Dr. Xiong said in the news release. That’s why, if it’s mutated, like in the mouse, cartilage and bone formation is disrupted – not halted. It’s also why neogenin could be a good therapeutic target for turning the tide on cartilage or bone loss that occurs in osteoarthritis, Dr. Xiong added.

Dr. Xiong told OTW,
My laboratory has been studying neogenin signaling for several years. Neogenin was initially identified as a receptor of netrin (neuronal axon guidance factor). However, its function in axon guidance seems minimal, as neogenin mutant embryo show relatively normal axon projections. We have studied neogenin signaling and function in several different cellular models, and have found that neogenin appears to be a regulator of BMP signaling in multiple cell types (Dae-Hoon Lee et al, Blood, 2010). This finding was also in light of the published observations of neogenin interacting with RGM proteins; RGMs appear to be BMP co-receptors. These observations led us to wonder if neogenin regulates cartilage development or chondrogenesis, which is largely dependent on BMP signaling. In addition, our studies were encouraged by the publications (by Cooper HM’s lab) that neogenin is highly expressed in cartilage or chondrocytes during embryonic development and that neogenin deficient mice are smaller.
She also commented to OTW,
We also want to address: 1) if neogenin regulates articular chondrocyte differentiation and function, as neogenin is also highly expressed in this type of chondrocytes (in adult stage). Understanding how neogenin functions in those chondrocytes would provide insight into our understanding of adult joint function and pathogenesis of arthritis; 2) if neogenin regulates osteoblast differentiation and function. Addressing if and how neogenin regulates osteoblast function would help us to not only understand normal bone formation, but also pathogenesis of osteoporosis. Perhaps those studies will help us to determine if neogenin can be a new drug-able target for treatment of osteoarthritis and osteoporosis.