High mobility group box-1 (HMGB-1) in osteoarthritic cartilage.
OBJECTIVE
Nucleosomal high mobility group box-1 (HMGB-1) is translocated and released from necrotic and activated cells as an endogenous danger signal (alarmin) and cytokine. It was hypothesised that it plays a role in osteoarthritis (OA). characterised by cellular activation, inflammation and enchondral bone formation.


METHODS
Bovine knee joint samples, collected from culled animals, were scored using histologic/histochemical grading to intact looking, mild, moderate or severe and immunohistochemically stained for HMGB-1. Chondrocyte pellets, produced from human bone marrow-derived mesenchymal stem cells and stimulated with tumour necrosis factor-a (TNF-alpha), were similarly stained.


RESULTS
In healthy looking OA cartilage chondrocyte nuclei were usually HMGB-1 negative and in mild OA staining was restricted to nuclei. In moderate OA lesions HMGB-1 was also seen in the cytoplasm and occasionally pericellular matrix and in severe OA lesions often also in intra- and inter-territorial matrix. The tidemark in healthy cartilage did not contain HMGB-1, which however was seen at this interface as linear deposits even in intact-looking and mild OA lesions, as multiple wave-like deposits in moderate and as heavy granular deposits in severe lesions. TNF-alpha stimulation of chondrocytes caused translocation of HMGB-1 from the nucleus to the cytoplasm.


CONCLUSIONS
In resting chondrocytes tight nucleosomal HMGB-1 binding might cause steric hindrance of immunostaining. TNF-alpha- or OA-mediated activation leads to nuclear staining and cytoplasmic translocation. Advancing OA leads to increasingly intense extra-/pericellular deposition of HMGB-1 alarmin, indicating local chondrocyte activation and/or necrosis. In particular, HMGB-1 at the tidemark might play a role in the pathological thickening of subchondral bone plate/osteophyte formation.
Heinola
T
T
Department of Medicine/Invärtes Medicin, Helsinki University Central Hospital, Helsinki, Finland. teppo.heinola@gmail.com
Kouri
V-P
VP
Clarijs
P
P
Ciferska
H
H
Sukura
A
A
Salo
J
J
Konttinen
Y T
YT
D000818:Animals; D001692:Biological Transport; D015415:Biomarkers; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002417:Cattle; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism*; D023421:Models, Animal; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015415:Biomarkers; D024243:HMGB1 Protein; D014409:Tumor Necrosis Factor-alpha