Interleukin-10 knockout mouse: a model for studying bone metabolism during intestinal inflammation.

Abstract

The objective was to compare bone mass (bone mineral content [BMC], bone mineral density [BMD]) and biomechanical strength of femurs and lumbar vertebrae from male and female wild-type (WT) and IL-10 knockout (KO) mice to determine if the IL-10 KO mouse model is appropriate for studying inflammation-associated bone abnormalities and potential interventions. Offspring from IL-10 KO and WT mice (n = 15 to 19 mice/gender per group) were studied until 13 weeks of age. IL-10 KO mice had a higher (P < 0.05) colonic histologic injury score and serum proinflammatory cytokines (IL-6, IL-1beta, TNF-alpha) than WT mice. IL-10 KO mice also experienced bone abnormalities as femur and verterbral BMC and BMD were lower (P < 0.05) compared with WT mice. Moreover, some biomechanical strength parameters such as femur yield load (P = 0.057) and resilience (P < 0.05) and peak load of lumbar vertebra 3 (P < 0.05) were lower than WT mice. Due to differences in body size, males had greater (P < 0.05) femur and vertebral bone mass as well as femur weight, length, yield load, resilience, and peak load than females. A significant interaction (genotype x gender) was only observed for femur resilience in which male WT mice had a greater (P = 0.009) resilience than all other groups. These results demonstrate that IL-10 KO mice develop bone abnormalities that accompany intestinal inflammation and elevated serum proinflammatory cytokines. Thus, the IL-10 KO mouse model may be useful for studying inflammation-associated bone abnormalities and potential therapeutic interventions.