Coupling of small leucine-rich proteoglycans to hypoxic survival of a progenitor cell-like subpopulation in Rhesus Macaque intervertebral disc.

Abstract

Degeneration of the intervertebral disc (IVD) is a major spinal disorder that associates with neck and back pain. Recent studies of clinical samples and animal models for IVD degeneration have identified cells with multi-potency in the IVD. However, IVD tissue-specific progenitor cells and their niche components are not clear, although degenerated IVD-derived cells possess in vitro characteristics of mesenchymal stromal cell (MSCs). Here, we firstly identified the tissue-specific intervertebral disc progenitor cells (DPCs) from healthy Rhesus monkey and report the niche components modulated the survival of DPCs under hypoxia. DPCs possess clonogenicity, multipotency and retain differentiation potential after extended expansion in vitro and in vivo. In particular, the nucleus pulposus-derived DPCs are sensitive to low oxygen tension and undergo apoptosis under hypoxic conditions due to their inability to induce/stabilize hypoxia-inducible factors (HIF). The presence of small leucine-rich proteoglycans (SLRP), biglycan or decorin, can reduce the susceptibility of DPCs to hypoxia-induced apoptosis via promoting the activation/stabilization of HIF-1α and HIF-2α. As IVD is avascular, we propose SLRPs are niche components of DPCs in IVD homeostasis, providing new insights in progenitor cell biology and niche factors under a hypoxic microenvironment.