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TB Meningitis, Reactive Oxygen Species (ROS) and the Pathological Ossification of the Petroccipital Fissure and Cochlear Cannaliculus
Author(s) -
Balboni Armand L,
Bergemann Andrew D,
Laitman Jeffrey T
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.647.10
Subject(s) - reactive oxygen species , ossification , oxidative stress , medicine , pathology , apoptosis , chondrocyte , microbiology and biotechnology , biology , anatomy , cartilage , biochemistry
Fibrocartilage ossification is a well‐controlled process in which chondrocytes within the tissue stop proliferating and differentiate into hypertrophic chondrocytes before undergoing apoptosis and the induction of tissue mineralization. We previously reported a pathological ossification of the fibrocartilagenous petroccipital fissure (POF) and cochlear cannaliculus (CC) in individuals with TB meningitis (Balboni et al., 2008). However, a mechanism by which such ossification could occur has not been shown. Recent work by Yang et al. (2007) demonstrates that TB meningitis causes a marked increase in the production of ROS in the central nervous system. To test whether an increase in ROS could cause POF/CC ossification we cultured ATDC5 chondrocytes in the presence of control medium(low ROS activity), differentiation medium(high ROS activity), or differentiation medium plus the antioxidant Deferiprone®, and observed them for evidence of hypertrophy. ATDC5 cells were also tested for the expression of the hypertrophic markers mmp13, typeX collagen, and runx2 via RT‐PCR. We show that increased ROS levels induce chondrocyte hypertrophy in vitro. Markers of elevated ROS levels are detected in hypertrophic ATDC5 chondrocytes while Deferiprone® protects cells from oxidative stress and inhibits these markers. These data demonstrate that POF/CC ossification could occur via ROS formed during TB meningitis. Grant Funding Source Faculty Research Award