Targeting GDF15 as a potential therapy for low back pain originating from endplate

Abstract

The overactivation of osteoclasts in the endplate is one of the most important causes of low back pain (LBP) originating from endplate. Transforming growth factor-{beta} family has been demonstrated to play an important role during osteoclast differentiation. GDF15 was reported to participate in several pathological states. In this study, we reported that the lumbar spine instability (LSI) induced the overactivation of osteoclasts and CD31hiEmcnhi endothelial vessels in the bony endplate. In addition, the expression of GDF15 in human disc samples and mice models were also increased. GDF15 could promote the fusion of preosteoclasts via Rac1/Cdc42/PAK/Cofilin axis, and facilitate the angiogenesis via the secretion of PDGF-BB. Furthermore, we proved that the GDF15 inhibitor, CTL-002 could reduce the expression of GDF15 in the endplate and alleviate the overactivation of osteoclasts and CD31hiEmcnhi endothelial vessels induced by LSI in vivo. In conclusion, we demonstrated that GDF15 could regulates the fusion of preosteoclasts and targeting GDF15 in the endplate served as a novel anabolic therapy for low back pain treatment.