Effects of long-term estrogen replacement therapy on articular cartilage IGFBP-2, IGFBP-3, collagen and proteoglycan levels in ovariectomized cynomolgus monkeys.
OBJECTIVE
The purpose of this study was to determine the effects of long-term estrogen replacement therapy (ERT) on insulin-like growth factor binding protein (IGFBP)-2, IGFBP-3, collagen and proteoglycan levels in the articular cartilage of the knee joint in a well-characterized monkey model of naturally occurring osteoarthritis (OA). A secondary aim was to evaluate the effect of soy phytoestrogen treatment on these articular cartilage components.


METHODS
Monkeys were ovariectomized and given ERT, soy phytoestrogen treatment or no treatment (control) for 3 years. Ten animals were randomly selected from each of the three groups and the cartilage was dissected from the proximal tibia and distal femur of the knee. Levels of IGFBP-2, IGFBP-3, and total protein were measured in cartilage desorptions, and proteoglycan levels and collagen levels were measured in the cartilage tissue. Sections from the tibial plateau of the opposite knee were immunostained using antibodies directed against IGFBPs and evaluated subjectively.


RESULTS
IGFBP-3 levels were significantly higher, and total protein levels were significantly lower in the cartilage desorption samples from the estrogen-treated animals compared to the control animals. There were no significant differences in IGFBP-2, collagen or proteoglycan levels between the estrogen-treated and control groups. Soy phytoestrogen treatment had no significant effect on the levels of any of the cartilage components that were measured. The staining patterns observed by immunohistochemistry suggested local production of IGFBP-2 and IGFBP-3 by articular cartilage chondrocytes.


CONCLUSIONS
Long-term estrogen treatment results in increased IGFBP-3 levels in articular cartilage without a significant change in IGFBP-2, collagen or proteoglycan content, and IGFBP-3 appears to be synthesized by articular cartilage chondrocytes. Long-term soy phytoestrogen treatment did not have a statistically significant effect on the levels of IGFBP-2, IGFBP-3, collagen or proteoglycan.
Ham
K D
KD
College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA. hamx0012@umn.edu
Oegema
T R
TR
Loeser
R F
RF
Carlson
C S
CS
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000032:analysis*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D005269:Femur / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000032:analysis*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis*; D007529:Isoflavones / Q000627:therapeutic use; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism; D008252:Macaca fascicularis; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000378:metabolism*; D010052:Ovariectomy; D048789:Phytoestrogens; D028321:Plant Preparations / Q000627:therapeutic use; D011506:Proteins / Q000032:analysis; D011509:Proteoglycans / Q000032:analysis*; D013025:Glycine max; D013977:Tibia / Q000378:metabolism
D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D011506:Proteins; D011509:Proteoglycans; D003094:Collagen