JBC Highlights Work of GSDM Trackman Lab
Dr. Philip Trackman has demonstrated, for the first time, that lysyl oxidase-like-2 is critical for normal cartilage formation.
The lysyl oxidase family is made up of five members, or isoforms: lysyl oxidase (LOX) and lysyl oxidase-like 1 – 4. All five isoforms share similarities that are expressed in lysyl oxidase or lysyl oxidase-like enzyme activity. It is widely understood that this activity plays a role in normal bone development, however until now the specific role of each of the isoforms remained largely unexplored.
Enter Mussadiq Iftikhar ORAL BIO 10, PERIO 10 and Paola Hurtado ORAL BIO 08, PERIO 12, two students working in Dr. Trackman’s lab—that with the guidance of Dr. Trackman, Research Assistant Professor Dr. Manish Bais, and BU School of Medicine Professor Dr. Louis Gerstenfeld—set out to evaluate the expression of all five isoforms in fracture healing.
The researchers determined the expression pattern of lysyl oxidase and its isoforms during fracture repair by collecting samples from mouse fractured femur calluses. After analyzing the samples, they determined that the expression pattern for lysyl oxidase-like-2 was different from the rest. Lysyl oxidase-like-2’s pattern spiked seven days after the fracture, which after further analysis, was determined to be the same time that the cartilage begins reforming. Most important, prevention of expression of lysyl oxidase like-2 with siRNA technology in a chondrocyte cell line completely prevented the chondrocyte differentiation program, thereby proving the critical role of lysyl oxidase like-2 in particular to cartilage formation.
Dr. Trackman futher explained the importance of this discovery, “This is the first normal biological function definitively identified for lysyl oxidase like-2, and contributes to a greater understanding of the biosynthesis of extracellular matrix and endochondral bone.”
The paper, “Lysyl Oxidase-like-2 (LOXL2) Is a Major Isoform in Chondrocytes and Is Critically Required for Differentiation,” can be found in full on the JBC website.