A comparative analysis of TonEBP conditional knockout mouse models reveals inter-dependency between compartments of the intervertebral disc

Abstract

Interactions between notochord and sclerotome are required for normal embryonic spine patterning, but whether the postnatal derivatives of these tissues also require interactions for postnatal intervertebral disc (IVD) growth and maintenance is less established. We report here the comparative analysis of four conditional knockout mice deficient for TonEBP/Nfat5, a transcription factor known to allow cells to adapt to changes in extracellular osmotic pressure, in specific compartments of the IVD. We show that TonEBP deletion in nucleus pulposus (NP) cells does not affect their survival or aggrecan expression, but promoted cell proliferation in the NP and in adjacent vertebral growth plates (GP). In cartilage end plates/GPs, TonEBP deletion induced cell death, but also structural alterations in the adjacent NPs and vertebral bodies. Embryonic or postnatal TonEBP loss generated similar IVD changes. In addition to demonstrating the requirement of TonEBP in the different compartments of the IVD, this comparative analysis uncovered the in vivo interdependency of the different IVD compartments during the growth of the postnatal IVD-vertebral units.