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Reduced cortical bone mass in mice with inactivation of interleukin-4 and interleukin-13
Carl-Johan Silfverswärd1, Sune Larsson, Claes Ohlsson
1Department of Surgical Sciences, University of Uppsala, S-751 85 Uppsala, Sweden.
Abstract:
The aim of the present study was to study the in vivo role of IL-4 and IL-13 on bone metabolism. The skeletal phenotypes of male and female IL-13(-/-) (n = 7+7), IL-4(-/-)IL-13(-/-) (n = 7+7), and WT (n = 7+7) mice were compared. Analysis was made at 6 weeks of age (juvenile) by pQCT, and at 20 weeks of age (adult) by pQCT, biomechanical testing, and by S-IGF-1 and S-Osteocalcin measurements. The skeletal phenotype was affected only in adult male IL-4(-/-)IL-13(-/-) mice. These animals displayed a reduction in cortical bone mineral content (BMC) of both the tibia and the femur, as measured by mid-diaphyseal pQCT scans, compared with WT mice (tibia -8.2%; femur -8.5%; p < 0.01). This reduction in cortical BMC was due to a decreased cross-sectional area as a result of a reduced cortical thickness. The mechanical strength of the cortical bone, tested by three-point-bending at the mid-diaphyseal region of the femurs, demonstrated a significant reduction of displacement at failure (-11.4%), maximal load at failure (-10.6%), and total energy until failure (-29.4%). S-IGF-1 and S-Osteocalcin levels as well as trabecular bone mineral density (tvBMD) were unaffected in adult male IL-4(-/-)IL-13(-/-) mice. IL-4(-/-)IL-13(-/-) male mice show adult onset reduction of cortical bone mass and strength, indicating that the two anti-inflammatory Th(2) cytokines IL-4 and IL-13 are involved in the regulation of bone remodeling.
Insights
Interleukin-4 (IL-4) and Interleukin-13 (IL-13) impact bone metabolism. Adult male mice lacking both IL-4 and IL-13 showed reduced cortical bone mass and strength, indicating their role in bone remodeling.
Area of Science:
- Immunology
- Bone Biology
- Endocrinology
Background:
- Interleukin-4 (IL-4) and Interleukin-13 (IL-13) are key anti-inflammatory cytokines.
- Their precise roles in adult bone metabolism in vivo remain incompletely understood.
Purpose of the Study:
- To investigate the in vivo function of IL-4 and IL-13 in regulating bone metabolism.
- To compare the skeletal phenotypes of mice lacking IL-13 or both IL-4 and IL-13 with wild-type controls.
Main Methods:
- Skeletal phenotypes were assessed in juvenile and adult male and female mice lacking IL-13 or both IL-4 and IL-13 (IL-4(-/-)IL-13(-/-)) using micro-computed tomography (pQCT).
- Adult mice underwent biomechanical testing (three-point bending) and serum analysis for Insulin-like Growth Factor 1 (S-IGF-1) and Osteocalcin (S-Osteocalcin).
Main Results:
- Adult male IL-4(-/-)IL-13(-/-) mice exhibited significantly reduced cortical bone mineral content (BMC) in the tibia and femur compared to wild-type mice.
- This reduction was attributed to decreased cortical thickness, leading to diminished cortical bone strength, including lower maximal load and energy absorption.
- Serum levels of S-IGF-1, S-Osteocalcin, and trabecular bone mineral density (tvBMD) were unaffected in these mice.
Conclusions:
- The combined absence of IL-4 and IL-13 leads to an adult-onset reduction in cortical bone mass and mechanical strength in male mice.
- These findings highlight a critical role for IL-4 and IL-13 in the regulation of bone remodeling in adult males.
