title: Selenium Reduces Early Signs of Tumor Necrosis Factor Alpha-Induced Meniscal Tissue Degradation.
abstract: Meniscal integrity is a prerequisite for sustained knee joint health and prevention of meniscal degeneration is a main research goal. Cartilage-protective effects of selenium have been described, but little is known about the impact on the meniscus. We therefore investigated the influence of sodium selenite on meniscal explants under tumor necrosis factor-alpha (TNFα)-stimulated proinflammatory conditions. Meniscal explant disks (3 mm diameter × 1 mm thickness) were isolated from 2-year-old cattle and incubated with TNFα (10 ng/ml) and sodium selenite (low dose, LoD 6.7 ng/ml as being found in Insulin-Transferrin-Selenium medium supplements, ITS; medium-dose, MeD 40 ng/ml described as physiological synovial concentration; high dose, HiD 100 ng/ml described as optimal serum concentration). After 3 days of culture glycosaminoglycan (GAG) release (DMMB assay), nitric oxide (NO) production (Griess assay), gene expression of matrix-degrading enzymes (quantitative RT-PCR), and apoptosis rate were determined. TNFα led to a significant raise of GAG release and NO production. LoD and MeD selenite significantly reduced the TNFα-induced GAG release (by 83, 55 %, respectively), NO production (by 59, 40 %, respectively), and apoptosis (by 68, 39 %, respectively). LoD and MeD selenite showed a tendency to reduce the TNFα-mediated increase of inducible NO-synthase (iNOS) levels, LoD selenite furthermore matrix metalloproteinase (MMP)-3 transcription levels and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 levels. LoD and less pronounced MeD selenite show a substantial impact on the early meniscal inflammatory response. To our knowledge this is the first study showing the protective influence of selenium on meniscal tissue maintenance. To understand the superior potency of low-dose selenium on molecular level future studies are needed.
authors: Christian-Albrechts-Universität zu Kiel, Anatomisches Institut, Otto-Hahn-Platz 8, 24118, Kiel, Germany. k.haefelein@anat.uni-kiel.de.
authors: Klaus
authors: http://orcid.org/0000-0002-9600-4940
authors: K
authors: Häfelein
authors: Christian-Albrechts-Universität zu Kiel, Anatomisches Institut, Otto-Hahn-Platz 8, 24118, Kiel, Germany.
authors: Andrea
authors: A
authors: Preuße-Prange
authors: Uniklinikum Schleswig-Holstein, Klinik für Orthopädie und Unfallchirurgie, Kiel, Germany.
authors: Peter
authors: P
authors: Behrendt
authors: Christian-Albrechts-Universität zu Kiel, Anatomisches Institut, Otto-Hahn-Platz 8, 24118, Kiel, Germany.
authors: Bodo
authors: B
authors: Kurz
mesh_terms: D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D000072600:Meniscus / Q000187:drug effects* / Q000378:metabolism*; D012643:Selenium / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D012643:Selenium
keywords: Meniscus; Selenite; Selenium; Supplementation; TNF-alpha