Johnson ZI, Shapiro IM, Risbud MV. (2016) RNA Sequencing Reveals a Role of TonEBP Transcription Factor in Regulation of Pro-inflammatory Genes in Response to Hyperosmolarity in Healthy Nucleus Pulposus Cells: A HOMEOSTATIC RESPONSE? J Biol Chem 291(52):26686.
This study shows that TonEBP an osmoregulatory transcription factor also controls expression of several inflammatory and catabolic genes in nucleus pulposus
Choi H, Merceron C, Mangiavini L, Seifert EL, Schipani E, Shapiro IM, Risbud MV. (2016) Hypoxia promotes noncanonical autophagy in nucleus pulposus cells independent of MTOR and HIF1A signaling. Autophagy 12(9):1631.
This study, for the first time, demonstrates that NP cells do not regulate autophagy through HIF-1α under hypoxia, and that this autophagy is also uniquely MTOR-independent.
Li J, Yuan W, Jiang S, Ye W, Yang H, Shapiro IM, Risbud MV. (2015) Prolyl-4-hydroxylase domain protein 2 controls NF-κB/p65 transactivation and enhances the catabolic effects of inflammatory cytokines on cells of the nucleus pulposus. J Biol Chem 290(11):7195.
We clearly demonstrated that PHD2 forms a regulatory circuit with TNF-α via NF-κB, and therefore may play an important role in enhancing this pro-inflammatory signal during disc degeneration.
Merceron C, Mangiavini L, Robling A, Wilson TL, Giaccia AJ, Shapiro IM, Schipani E, Risbud MV. (2014) Loss of HIF-1α in the notochord results in cell death and complete disappearance of the nucleus pulposus. PLoS One 9(10):e110768.
This is the first report describing phenotype of NP-specific HIF-1α knockout mice. This study unequivocally demonstrates that HIF-1α is essential for NP cell survival and maintaining the tissue homeostasis.
Hirose Y, Johnson ZI, Schoepflin ZR, Markova DZ, Chiba K, Toyama Y, Shapiro IM, Risbud MV. (2014) FIH-1-Mint3 axis does not control HIF-1 transcriptional activity in nucleus pulposus cells. J Biol Chem 289(30):20594.
This study shows that FIH-1 activity does not regulate HIF-1-dependent transcription in NP cells, possibly as an adaptation to their unique hypoxic niche.
Class i and IIa HDACs Mediate HIF-1α Stability Through PHD2-Dependent Mechanism, while HDAC6, a Class IIb Member, Promotes HIF-1α Transcriptional Activity in Nucleus Pulposus Cells of the Intervertebral Disc