Pramlintide regulation of extracellular matrix (ECM) and apoptosis through mitochondrial-dependent pathways in human nucleus pulposus cells.

Pramlintide, an approved analog of amylin, is responsible for regulating the physiology of energy homeostasis. The goals of this study were to investigate the roles of pramlintide in the regulation of cell survival and matrix metabolism, and further explore their underlying mechanisms, in human nucleus pulposus (NP) cells. NP cells were treated with different concentrations of pramlintide in normoxic or hypoxic conditions. Cell viability, LAC concentration, calcium concentration, mitochondrial membrane potential (ΔΨm), MMPs proteins, and apoptotic related proteins were detected. The results indicate that pramlintide could improve NP cell proliferation, glycolytic activity, and the ECM synthesis under hypoxia, which is evident from the increased precipitation of proteoglycans; increased expression of AGG, Col2, and SOX9 proteins; and decreased expression of MMP3, MMP9, and MMP13 proteins, which are Ca2+-dependent enzymes. And, pramlintide could facilitate the survival of NP cells through mitochondrial-mediated, Bcl-2/caspase-3-dependent apoptosis. In addition, activation of AKT-AMPK/mTOR signaling pathway is also observed by the treatment. These findings demonstrate that pramlintide may play a pivotal role in reversing intervertebral disk degeneration and may relieve the impairment of ECM metabolism and NP cells survival through mitochondrial-dependent apoptotic signaling pathway, thus offering a novel potential pharmacological treatment strategy.