PAPER 107: INTERVERTEBRAL DISC AND ARTICULAR CARTILAGE DEGENERATION IN MICE LACKING EARLY GROWTH RESPONSE PROTEIN-1 (EGR-1)

Abstract

Purpose: It has been shown that ischemic/hypoxic stress as well as shear stress and mechanical injury are linked to the pathogenesis of osteoarthritis. The aim of this study was to determine whether Egr-1 (Early Growth Response protein-1), a transcription factor induced by stress or injury, affects articular cartilage and intervertebral discs (IVDs).

Method: Experimental studies used 6- to 7-month-old adult female wild-type C57Bl/6 or Egr-1-deficient (knockout) 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: Results showed that the articular cartilage of knee joints of Egr-1 knockout mice was more irregular and degenerative than in the wild type mice. Furthermore, a lower concentration of proteoglycans (predominantly aggrecan) was observed in articular cartilage of knockout mice. The nucleus pulposus (NP) of the knockout mice IVD also showed signs of degeneration and a loss of notochordal cells. The overall disc height was also reduced compared to wild type mice. The number of cells in the endplate was higher in the knockout mice than in the wild type animals. Furthermore, there was a trend for increased lumbar vertebrae BMD as well a significant increase in BMD in the femur of the Egr-1 knockout mice. The relative bone volume (BV/TV) was significantly smaller in Egr-1 knockout mice as was trabecular number and trabecular separation, while there was increased bone surface to bone volume.

Conclusion: Our findings showed signs of degeneration in both articular cartilage and IVD in Egr-1 knockout mice. Moreover, the loss of height in IVD and cellular components of the NP, as well as the increased cell numbers in cartilage of the endplate showed some resemblance to those of human degenerative disc diseases. However, further studies are needed to determine the mechanism by which Egr-1 leads to articular cartilage and IVD degeneration.