Changes in the size of hyperthrophic chondrocytes in articular cartilage in osteoarthritis

Abstract

Purpose: Osteoarthritis (OA) is a disease characterized by degradation of articular cartilage, osteophyte formation, subchondral sclerosis and synovial proliferation, which results in the loss of joint function and disability. Osteoporosis (OP) is a disorder characterized by reduced bone mass, leading to diminished physical bone strength and increased susceptibility to fracture. In a combined model of OP followed by a destabilization-induced OA in rabbits, we have described microstructural impairment of subchondral bone withincreased remodelling that aggravates cartilage damage. Accordingly, numerous alterations in structural and biomechanical properties have been described in the articular cartilage of different experimental models of low bone mass induced by ovariectomy (OVX). Our aim was to associate the severity of OA and the size of the hyperthropic chondrocytes in articular cartilage in a combined model of OPOA. Methods: New Zealand female rabbits were randomly assigned to four groups: healthy rabbits (control group, n=8), osteoporotic (OP group, n=7), osteoarthritic (OA group, n=8) and OA with previous osteoporosis rabbits (OPOA group, n=8). OP was induced by OVX and administration of metilprednisolone (1mg/kg/day) during six weeks. After this period, OA was induced by anterior cruciate ligand transection and the disease developed over 6 weeks. All animals were euthanized and tibias, femurs, synovium and serum samples were collected. 17-beta estradiol levels were analyzed for OP validation. Macroscopic evaluation and Mankin score were done to analyze joint damage. TRAP staining was performed in the joint to analyze bone resorption. Finally, chondrocyte size was measured in articular cartilage, and we did a correlation between the chondrocyte size and the Mankin score. To carry out statistic studies we used a Kruskal-Wallis test following by a Mann Whitney test. Results: OP induced-rabbits showed lower levels of 17-beta estradiol (pg/ml) than the others (Healthy: 44±8, OP: 26±3, OA: 40±10, OPOA: 28±6, p<0.05 OP and OPOA vs Healthy). Macroscopic evaluation reflected significant differences between control and the rest of the groups, and between OA and OPOA faced to OP (Healthy: 0.25±0.10, OP: 2.0±0.5, OA: 4.6±0.2, OPOA: 4.5±0.2, p<0.05 all groups vs Healthy, and OA-OPOA vs OP). Mankin score showed significant more severity damage in osteoarthritic groups than control rabbits, and OPOA more than OP group (Healthy: 1.6±0.2. OP: 5.0±1.5, OA: 6.0±0.6, OPOA: 7.5±1.3, p<0.05 vs Control). TRAP staining showed that OA and OPOA groups had more number of stained cells than Control and OP rabbits (Healthy: 8.5+2.6, OP: 7.6±3.0, OA: 43±11, OPOA: 80±18). Osteoarthritic groups had larger chondrocyte size than control and OP rabbits, and OPOA chondrocytes were slightly larger than OA chondrocytes. (Healthy: 131±7, OP: 152±12, OA: 187±15, OPOA: 234±16, p<0.005 OA - OPOA vs Healthy, p<0.05 OPOA vs OA). Finally, it was significantly the correlation between Mankin score and chondrocyte size(p<0.05, r= 0.4314). Conclusions: Our results suggest that OPOA model presents more severity than OA in joint damage, and this fact correlated with chondrocyte size in articular cartilage, whose are associated in osteoarthritis with the severity of the disease, being bigger in OPOA rabbits than OA group.