Abstract
Both age and intensive exercise are generally considered critical risk factors for osteoarthritis. In this work, we intend to establish zebrafish models to assess the role of these two factors on cartilage homeostasis. We designed a swimming device for zebrafish intensive exercise. The body measurements, bone mineral density (BMD) and the histology of spinal cartilages of 4- and 12-month-old zebrafish, as well the 12-month-old zebrafish before and after a 2-week exercise were compared. Our results indicate that both age and exercise affect the body length and body weight, and the micro-computed tomography reveals that both age and exercise affect the spinal BMD. However, quantitative analysis of immunohistochemistry and histochemistry indicate that short-term intensive exercise does not affect the extracellular matrix (ECM) of spinal cartilage. On the other hand, the cartilage ECM significantly grew from 4 to 12 months of age with an increase in total chondrocytes. dUTP nick end labeling staining shows that the percentages of apoptotic cells significantly increase as the zebrafish grows, whereas the BrdU labeling shows that proliferative cells dramatically decrease from 4 to 12 months of age. A 30-day chase of BrdU labeling shows some retention of labeling in cells in 4-month-old spinal cartilage but not in cartilage from 12-month-old zebrafish. Taken together, our results suggest that zebrafish chondrocytes are actively turned over, and indicate that aging is a critical factor that alters cartilage homeostasis. Zebrafish vertebral cartilage may serve as a good model to study the maturation and homeostasis of articular cartilage.
Highlights
Osteoarthritis (OA) is the most common pathologic condition of articular cartilage and leads to joint pain and stiffness, degeneration of articular cartilage and, sometimes, ectopic osteogenesis to form osteophytes
Zebrafish continues to grow after sexual maturity while intensive exercise hinders this growth In mammals, hormones such as estrogen fluctuate dramatically during sexual maturity and trigger the halt in skeletal growth including the closure of epiphyseal plates in bones (Zhong et al, 2011)
The body measurements of zebrafish indicate that zebrafish continues to grow after sexual maturity as the body length increased significantly from 2.65 cm at 4 months of age to 3.12 cm (Fig. 1C; Table S2)
Summary
Osteoarthritis (OA) is the most common pathologic condition of articular cartilage and leads to joint pain and stiffness, degeneration of articular cartilage and, sometimes, ectopic osteogenesis to form osteophytes. The superficial zone contains the highest cell density and the superficial cells secret proteoglycan 4 as a joint lubricant. These cells have a large long/short morphological axis ratio (Schumacher et al, 1994). The middle zone accounts for the major volume of an articular cartilage and the middle cells are enlarged, with an oval shape, usually sitting in lacunae compared to the superficial cells (Hedlund et al, 1999). The deep cells are usually round hypertrophic chondrocytes, while the calcified zone is a transition region between cartilage and subchondral bone (Grogan et al, 2009; Schmid & Linsenmayer, 1985)
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