PAPER 109: EFFECT OF ESTROGEN DEFICIENCY ON ARTICULAR CARTILAGE AND INTERVERTEBRAL DISC OF MICE

Abstract

Purpose: Hormone replacement therapy for the menopause seems to be associated with a decrease in the prevalence of symptoms and radiological alterations related to hip and knee osteoarthritis. However, little is known on the effects of estrogen in articular cartilage and intervertebral disc (IVD). The aim of this study was to evaluate the developmental changes in mouse articular cartilage and intervertebral discs under estrogen deficiency.

Method: Experimental studies used 6- to 7-month-old adult female wild-type or bilaterally ovariectomized (OVX) C57Bl/6 mice. All animals were sacrificed at the same age interval (8- to 9-months) and stored at −20°C. Prior to dissection, posterior-anterior and lateral x-rays of whole mice were done. Right knee joint and cervical to lumbar spine were stained with hematoxylineosin (H& E), Safranin-O/Fast green, and Weigert’s hematoxylin/alcian blue/picrosirius red for histological analysis. Bone mineral density (BMD) was measured using a PIXImus Bone Densitometer System. Micro computed tomography (CT) data were acquired on a SkyScan T1072 X-ray Microscope-Microtomograph.

Results: Degeneration, including the loss of notochordal cells, was observed in the nucleus pulposus (NP) of the IVD of OVX mice. The annulus fibrosus (AF) showed marked thinning as compared to the wild type. Furthermore, the OVX group showed decreased IVD heights and trend of endplate ossification. Knee joints of OVX mice showed a trend towards having more gross degenerative changes, like areas of cartilage erosion. A decrease in articular cartilage thickness was also observed. Certain layers of cartilage were more affected than others, suggesting a specific role of estrogens in the developing cartilage. Also, the BMD was reduced in both the femur and lumbar vertebrae of the OVX group. Finally, MicroCT results showed a decrease in percent bone volume, trabecular thickness, trabecular number, and an increase in trabecular separation.

Conclusion: The present study showed AF thinning, decreased IVD height, NP degeneration, and loss of cellular components in the NP in ovariectomized mice. Likewise, the articular cartilage revealed more degenerative changes, including a decrease in articular thickness. Results suggest that estrogens play a role in maintaining healthy cartilage and IVD.