Intercellular Signaling Pathways Active During Intervertebral Disc Growth, Differentiation, and Aging

Study Design. Intervertebral discs at different postnatal ages were assessed for active intercellular signaling pathways. Objective. To generate a spatial and temporal map of the signaling pathways active in the postnatal intervertebral disc (IVD). Summary of Background Data. The postnatal IVD is a complex structure, consisting of 3 histologically distinct components, the nucleus pulposus, fibrous anulus fibrosus, and endplate. These differentiate and grow during the first 9 weeks of age in the mouse. Identification of the major signaling pathways active during and after the growth and differentiation period will allow functional analysis using mouse genetics and identify targets for therapy for individual components of the disc. Methods. Antibodies specific for individual cell signaling pathways were used on cryostat sections of IVD at different postnatal ages to identify which components of the IVD were responding to major classes of intercellular signal, including sonic hedgehog, Wnt, TGF beta, FGF, and BMPs. Results. We present a spatial/temporal map of these signaling pathways during growth, differentiation, and aging of the disc. Conclusion. During growth and differentiation of the disc, its different components respond at different times to different intercellular signaling ligands. Most of these are dramatically downregulated at the end of disc growth.