The fate of chondrocyte in osteoarthritic cartilage of transgenic mice expressing bovine GH.
OBJECTIVE
The aim of the present study was to demonstrate whether bGH transgenic mice develop OA. We therefore studied in this animal model the structural features of cartilage and the subchondral bone changes of the knee joints that may be associated with osteoarthritic lesion.


METHODS
Degenerative changes in the knee joints of bGH transgenic female mice (N = 11) and control mice (N = 11) were histologically analyzed at the age of 7 months. Histochemical and stereological studies were conducted. Immunohistochemistry on cell cyclin activity (assessed by anti-PCNA labeling) and cell viability (assessed by bcl-2 expression), as well as ribosomal activity (AgNOR), TNF-alpha expression and apoptosis (TUNEL technique) were performed. In ten 7-month-old female mice (Tg+ N = 5; control N = 5) the knee articular cartilages were studied with electron microscopy techniques.


RESULTS
Disruption of the articular surface (18.2%), cleft (63.7%), cloning (81.8%), hypocellularity of chondrocytes (18.2%), moderate (54.6%) to severe (45.4%) loss of safranin-O staining, and duplication and rupture of the tidemark (54.5%) were some of the main features observed in articular cartilage chondrocytes of bGH transgenic mice. Furthermore, cell cyclin activity and cell viability decreased, while TNF-alpha expression and TUNEL+ cells increased. These chondrocytes also showed an increase in the number of black dots per cell, as revealed by the AgNOR technique.


CONCLUSIONS
Our results show that bGH transgenic mice develop a lesion of the articular cartilage consistent with that described in osteoarthritis.
Fernández-Criado
C
C
Gabinete de Veterinaria, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
Martos-Rodríguez
A
A
Santos-Alvarez
I
I
García-Ruíz
J P
JP
Delgado-Baeza
E
E
D000818:Animals; D001175:Arthrography / Q000379:methods; D002358:Cartilage, Articular / Q000503:physiopathology*; D002452:Cell Count; D019902:Chondrocytes / Q000502:physiology*; D005260:Female; D013006:Growth Hormone / Q000032:analysis*; D006614:Hindlimb; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007596:Joints / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron / Q000379:methods; D008859:Microscopy, Polarization / Q000379:methods; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*
D013006:Growth Hormone