K. Takahashi et al., ANALYSIS OF HEAT-SHOCK PROTEINS AND CYTOKINES EXPRESSED DURING EARLY STAGES OF OSTEOARTHRITIS IN A MOUSE MODEL, Osteoarthritis and cartilage, 5(5), 1997, pp. 321-329
Objective: Osteoarthritis (OA) is a debilitating disease of the joints
. The joints of affected individuals are characterized by a progressiv
e degeneration of articular cartilage leading to inflammation and pain
. The expression of heat shock proteins (HSPs) is a ubiquitous self-pr
otective mechanism of all cells under stress, furthermore, the synoviu
m of osteoarthritic individuals contains high levels of cytokines. Thi
s study seeks to establish the role of HSPs and cytokines in OA. METHO
DS: We have investigated the presence of HSPs and cytokines in articul
ar cartilage during early stages of OA in a mouse that is known to dev
elop spontaneous OA lesions (C57 black mouse). The articular cartilage
from closely related mice (C57BL/6) was used as control. Messenger RN
As (mRNAs) for HSPs (HSP32, HSP47, HSP60, HSP70, HSP84 and HSP86) and
cytokines [interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor
necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)] w
ere detected by reverse transcription-polymerase chain reaction (RT-PC
R). Results: The mRNA levels of HSP47, HSP70, HSP86, IL-6, and IFN-gam
ma were up-regulated in the cartilage of C57 black mice, whereas, the
level of expression of HSP32, HSP60, HSP84 and IL-1 beta remained unch
anged. Furthermore, the expression of IL-1 beta, IL-6, TNF-alpha and I
FN-gamma mRNA was associated with expression of HSP60, HSP47, HSP70 an
d HSP70/HSP86 mRNA, respectively. Conclusions: The findings in this st
udy suggest that chondrocytes are conditioned under non-physiological
stress during early stages of OA, In addition, among HSPs, HSP70 was a
ssociated with two different highly expressed cytokines in C57 black m
ice, indicating the possible role of HSP70 as a characteristic indicat
or of early stage of OA.