Tibial bone versican content decreases with zoledronate treatment in adult mice

Abstract

In bone remodeling, the expression and turnover of the proteoglycans versican and aggrecan are poorly understood. We report changes in adult mouse bone contents of versican and aggrecan associated with bothage and treatment with the drug zoledronate. The data may have implications for experimental animal models of osteoporosis and related conditions. Versican and aggrecan are large, aggregating proteoglycans involved in skeletal development, but little is known about their roles in bone remodeling. The purpose of this study was to investigate versican and aggrecan contents in adult mouse bones, and changes in their contents in response to the bisphosphonate zoledronate (ZOL). Mice (9weeks old) were treated with 125μg/kg ZOL or vehicle for 3 or 15weeks. Versican and aggrecan were isolated from tibial bones for Western blotting, automated integrated densitometry, and analysis (two-way ANOVA, α = 0.05). In ZOL-treated mouse bones, compared to vehicle, 340 and 60kDa versican content decreased significantly, and 100 and 60kDa aggrecan content decreased significantly (drug effect). In 24-week-old mouse bones, compared to 12weeks, statistically significant decreases were observed in 340, 80, 60, and 11kDa versican, and in 100, 70, and 40kDa aggrecan (age effect). There was a statistically significant ZOL-age interaction for 330kDa aggrecan. This is the first study to assess physiological versican and aggrecan adaptations in adult mammalian bone tissue, in the presence and absence of ZOL. We observed large decreases in some versican and aggrecan species from 12 to 24weeks. We also observed decreases in several versican and aggrecan species in the presence of ZOL. This indicates that bone proteoglycan expression and turnover may be important in bone remodeling.