Role of progranulin in endochondral ossification after spinal cord injury

Veterans Affairs Med Ctr San Francisco, San Francisco CA

Investigators

Abstract

DESCRIPTION (provided by applicant): Clinical consequences of spinal cord injury (SCI) have significant musculoskeletal morbidity. One complication, heterotopic ossification (HO), has an increased incidence of up to 20-30% in SCI patients. With HO, function can be impaired through loss of joint mobility and pain. Formation of HO is thought to be analogous to other examples of bone formation in the body, such as in fracture healing. Interestingly, SCI patients also show increased fracture callus after bony injury. Fracture healing occurs through endochondral ossification (EO) and there is evidence that HO does as well. Putting these two clinical scenarios together, it appears that SCI patients have an exaggerated EO response. In looking at growth factors that are associated with SCI and EO, Progranulin represents a potential target. Progranulin is upregulated after SCI and is associated with the BMP-2 pathway. We hypothesize that progranulin is responsible for the increased EO seen after SCI. We aim to test this hypothesis using proganulin knockout mice in a model of SCI, with experimental fracture or HO. Understanding the mechanism by which SCI patients produce excess EO can help to develop therapies to reduce HO in these patients and increase fracture healing in non-SCI patients.