The tandem–random transition of cellular patterning: Roles of N-cadherin-based orientational cell adhesions in the development, maintenance, and degeneration of the nucleus pulposus

Abstract

Abstract Intervertebral disc (IVD) degeneration can cause low back and neck pain. In IVD degeneration, the most affected component of IVDs is the nucleus pulposus (NP). Derived from the notochord, where cells organize into a tandem configuration, the NP contains cells clustered in 3-dimensional (3D) networks embedded in a gelatinous matrix. Here, we summarize the current understanding of NP development, homeostasis, physiology, and degeneration as well as the roles of cell adhesion molecule N-cadherin in these processes. We hypothesize that N-cadherin contributes to the architectural transition from the notochord to the NP by switching from mediating tandem orientational cell adhesions (OCAs) to random OCAs. The 3D clustering of NP cells may facilitate N-cadherin to act as a mechanosensor to modulate NP gene expression under mechanical stresses. We also highlight some open questions on N-cadherin functions in the NP. Answering these questions helps with developing measures to prevent and treat IVD degeneration.