The overall goal of the disc cell biology program is to introduce novel therapeutic agents and strategies to treat intervertebral disc degeneration in a minimally invasive manner to restore intervertebral disc structure, and to reduce painful conditions of degenerative disc disease. Current therapies fail to integrate both structural repair and analgesia so that developing new therapeutic agents and strategies are a major research priority.
ACCUMULATION AND LOCALIZATION OF MACROPHAGE PHENOTYPES WITH HUMAN INVERTEBRAL DISC DEGENERATION
The recently published manuscript in the Journal of Orthopaedic research assessed if chronic inflammatory conditions of IVD degeneration involve macrophages or macrophage-like cells. Results demonstrated increasing expression of multiple macrophage markers with intervertebral disc degeneration.
Accumulation and localization of macrophage phenotypes with human intervertebral disc degeneration Nakazawa KR, Walter BA, Laudier DM, Krishnamoorthy D, Mosley GE, Spiller KL, Iatridis JC. The Spine Journal , Volume 18, Issue 2, Pages 343-356 (February 2018) DOI: 10.1016/j.spinee.2017.09.018; PMID: 29031872
HYPEROSMOLARITY INDUCES NOTOCHORDAL CELL DIFFERENTIATION INTO NUCLEUS PULPOSUS CELLS
The recently published manuscript in the Journal of Orthopaedic Research identified osmolarity as a triggering mechanism for notochordal cell differentiation. Osmolarity changes were associated with shifts in osmoregulatory and mechanotransductive proteins, which likely play important roles in intervertebral disc aging
Hyperosmolarity induces notochordal cell differentiation with aquaporin3 upregulation and reduced N-cadherin expression. Palacio-Mancheno PE, Evashwick-Rogler TW, Laudier DM, Purmessur D, Iatridis JC. J Orthop Res. 2017 Aug 29. doi: 10.1002/jor.23715. [Epub ahead of print] PMID: 28853179
HYPOOSMOLARITY INCREASES PRO-INFLAMMATORY CYTOKINES IN INTERVERTEBRAL DISCS
The manuscript published in European Cells and Materials demonstrated that reduced tissue osmolarity can increase TRPV4 signaling and enhance pro-inflammatory cytokine production. The study used bovine IVDs from an inflammatory organ culture model to investigate if TRPV4 is expressed in the IVD and how expression changes with intervertebral disc degeneration. Results suggested that changes in TRPV4 mediated osmo-sensation might contribute to the progressive matrix breakdown in disease.
Reduced tissue osmolarity increases TRPV4 expression and pro-inflammatory cytokines in intervertebral disc cells. Walter BA, Purmessur D, Moon A, Occhiogrosso J, Laudier DM, Hecht AC, Iatridis JC. Eur Cell Mater. 2016 Jul 19;32:123-36. PMID: 27434269