INTRICACIES OF INTERVERTEBRAL DISC METABOLISM: LESSONS FROM ANIMAL MODELS

Nucleus pulposus (NP) cells of the intervertebral disc reside in a physiologically hypoxic niche and bioenergetically rely on anaerobic glycolysis generating lactate. Consequently, disc cells reside in an environment characterized by acidic pH. Pathologically acidic pH in NP cells has been shown to lead to matrix catabolism and decreased glucose uptake; therefore NP cells rely on robust HIF-1-dependent pH-regulating systems to maintain the optimal pH for cell survival. However, how disc cells handle high levels of lactate is not entirely understood. To address this long-standing question, we generated annulus fibrosus (AF) and endplate (EP) specific knockout mice for MCT1, a ubiquitously expressed channel involved in lactate influx. Our studies showed significant disc degeneration in knockout mice, characterized by NP cell loss and EP changes. Our studies provide the first in vivo evidence that metabolic coupling between disc compartments is essential for the growth and maintenance of health.