TY - JOUR A1 - Kameda, Takuya A1 - Zvick, Joel A1 - Vuk, Miriam A1 - Sadowska, Aleksandra A1 - Tam, Wai Kit A1 - Leung, Victor Y. A1 - Bölcskei, Kata A1 - Helyes, Zsuzsanna A1 - Applegate, Lee Ann A1 - Hausmann, Oliver N. A1 - Klasen, Juergen A1 - Krupkova, Olga A1 - Würtz-Kozak, Karin T1 - Expression and Activity of TRPA1 and TRPV1 in the Intervertebral Disc BT - Association with Inflammation and Matrix Remodeling JF - International journal of molecular sciences N2 - Transient receptor potential (TRP) channels have emerged as potential sensors and transducers of inflammatory pain. The aims of this study were to investigate (1) the expression of TRP channels in intervertebral disc (IVD) cells in normal and inflammatory conditions and (2) the function of Transient receptor potential ankyrin 1 (TRPA1) and Transient receptor potential vanilloid 1 (TRPV1) in IVD inflammation and matrix homeostasis. RT-qPCR was used to analyze human fetal, healthy, and degenerated IVD tissues for the gene expression of TRPA1 and TRPV1. The primary IVD cell cultures were stimulated with either interleukin-1 beta (IL-1) or tumor necrosis factor alpha (TNF-) alone or in combination with TRPA1/V1 agonist allyl isothiocyanate (AITC, 3 and 10 mu M), followed by analysis of calcium flux and the expression of inflammation mediators (RT-qPCR/ELISA) and matrix constituents (RT-qPCR). The matrix structure and composition in caudal motion segments from TRPA1 and TRPV1 wild-type (WT) and knock-out (KO) mice was visualized by FAST staining. Gene expression of other TRP channels (A1, C1, C3, C6, V1, V2, V4, V6, M2, M7, M8) was also tested in cytokine-treated cells. TRPA1 was expressed in fetal IVD cells, 20% of degenerated IVDs, but not in healthy mature IVDs. TRPA1 expression was not detectable in untreated cells and it increased upon cytokine treatment, while TRPV1 was expressed and concomitantly reduced. In inflamed IVD cells, 10 mu M AITC activated calcium flux, induced gene expression of IL-8, and reduced disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and collagen 1A1, possibly via upregulated TRPA1. TRPA1 KO in mice was associated with signs of degeneration in the nucleus pulposus and the vertebral growth plate, whereas TRPV1 KO did not show profound changes. Cytokine treatment also affected the gene expression of TRPV2 (increase), TRPV4 (increase), and TRPC6 (decrease). TRPA1 might be expressed in developing IVD, downregulated during its maturation, and upregulated again in degenerative disc disease, participating in matrix homeostasis. However, follow-up studies with larger sample sizes are needed to fully elucidate the role of TRPA1 and other TRP channels in degenerative disc disease. KW - low back pain KW - TRP channels KW - pro-inflammatory cytokines KW - aggrecanases KW - collagen KW - TRPA1 KW - TRPV1 KW - TRPV2 KW - TRPV4 KW - TRPC6 Y1 - 2019 U6 - https://doi.org/10.3390/ijms20071767 SN - 1422-0067 VL - 20 IS - 7 PB - MDPI CY - Basel ER - TY - JOUR A1 - Sadowska, Aleksandra A1 - Touli, Ermioni A1 - Hitzl, Wolfgang A1 - Greutert, Helen A1 - Ferguson, Stephen J. A1 - Würtz-Kozak, Karin A1 - Hausmann, Oliver N. T1 - Inflammaging in cervical and lumbar degenerated intervertebral discs BT - analysis of proinflammatory cytokine and TRP channel expression JF - European Spine Journal N2 - To investigate and compare the occurrence of inflammatory processes in the sites of disc degeneration in the lumbar and cervical spine by a gene array and subsequent qPCR and to investigate the mechanistic involvement of transient receptor potential channels TRPC6 and TRPV4. The gene expression of inflammatory cytokines and TRP channels was measured in human disc samples obtained from patients undergoing discectomy at the cervical (n = 24) or lumbar (n = 27) spine for degenerative disc disease (DDD) and disc herniation (DH) and analyzed for differences with regard to spinal level, IVD degeneration grade, Modic grade, age, sex, disc region and surgical extent. Aside from genes with known implication in DDD and DH, four previously unreported genes from the interferon and TRP families (IFNA1, IFNA8, IFNB1, TRPC6) could be detected. A correlation between gene expression and age (IL-15) and IVD degeneration grade (IFNA1, IL-6, IL-15, TRPC6), but not Modic grade, was identified. Significant differences were detected between cervical and lumbar discs (IL-15), nucleus and annulus (IL-6, TNF-alpha, TRPC6), single-level and multi-level surgery (IL-6, IL-8) as well as DDD and DH (IL-8), while sex had no effect. Multiple gene-gene pair correlations, either between different cytokines or between cytokines and TRP channels, exist in the disc. This study supports the relevance of IL-6 and IL-8 in disc diseases, but furthermore points toward a possible pathological role of IL-15 and type I interferons, as well as a mechanistic role of TRPC6. With limited differences in the inflammatory profile of cervical and lumbar discs, novel anti-inflammatory or TRP-modulatory strategies for the treatment of disc pathologies may be applicable independent of the spinal region. KW - Cervical and lumbar discs KW - Degenerative disc disease (DDD) and disc herniation (DH) KW - Inflammaging KW - Inflammation KW - Intervertebral disc KW - Transient receptor potential (TRP) channel Y1 - 2017 U6 - https://doi.org/10.1007/s00586-017-5360-8 SN - 0940-6719 SN - 1432-0932 VL - 27 IS - 3 SP - 564 EP - 577 PB - Springer CY - New York ER - TY - JOUR A1 - Wuertz-Kozak, Karin A1 - Bleisch, Dominique A1 - Nadi, Najia A1 - Proemmel, Peter A1 - Hitzl, Wolfgang A1 - Kessler, Thomas M. M. A1 - Gautschi, Oliver P. A1 - Hausmann, Oliver N. T1 - Sexual and urinary function following anterior lumbar surgery in females JF - Neurourology and urodynamics N2 - Aims Anterior lumbar interbody fusion procedures (ALIF) and total disc replacement (TDR) with anterior exposure of the lumbar spine entail a risk of a vascular injury and dysfunction of the sympathetic and parasympathetic nerves due to disturbance of the inferior and superior hypogastric plexus. While retrograde ejaculation is a known complication of the anterior spinal approach in males, post-operative sexual as well as urinary function in females has not yet been thoroughly investigated and was hence the aim of this study. Methods Fifteen female patients documented their sexual and urinary function preoperatively, 3 months and 6 months postoperatively, using the validated questionnaires FSFI (Female Sexual Function Index) and ICIQ (International Consultation of Incontinence Questionnaire). Randomization tests were used to statistically analyze expectation values over time (two-sided, P < 0.05). Results While no statistically significant change in the total FSFI score occurred over time, a significant increase in FSFI desire score was noted between preoperative (2.95 +/- 0.8) and 6 months follow-up (3.51 +/- 0.6, P = 0.02). Urinary continence remained unchanged over time. Conclusion In summary, ALIF and lumbar TDR do not seem to negatively influence sexual and urinary function in females. In contrast, increased sexual desire was noted, likely secondary to post-surgical pain relief. KW - ALIF KW - dysfunction KW - FSFI KW - ICIQ KW - questionnaire KW - TDR KW - women Y1 - 2018 U6 - https://doi.org/10.1002/nau.23874 SN - 0733-2467 SN - 1520-6777 VL - 38 IS - 2 SP - 632 EP - 636 PB - Wiley CY - Hoboken ER -