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Biological or Clinical Significance:

Osteoactivin, also known as transmembrane glycoprotein NMB (GPNMB) and dendritic cell-associated transmembrane protein (DC-HIL), is a type I transmembrane glycoprotein that is found either on the plasma membrane or on membranes of the endosome/lysosome compartment. The extracellular region of Osteoactivin contains a heparin-binding motif and an integrin recognition RGD domain, while the cytocylasmic region contains an immunoreceptor tyrosine-based activation motif (ITAM) and lysosomal targeting motif.

GPNMB was originally identified as a gene that was expressed in poorly metastatic human melanoma cell lines and xenografts and not expressed in highly metastatic cell lines. However, several recent studies have identified high GPNMB expression in aggressive melanoma, glioma, and breast cancer specimens. In addition, Osteoactivin (OA) could be a novel therapeutic agent used to treat generalized osteoporosis or localized osteopenia during fracture repair by stimulating bone growth and regeneration. Similarly, Osteoactivin expression increases during osteoclast differentiation and it is functionally implicated in this process, possibly by promoting the fusion of osteoclast progenitor cells.






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