Reduced cortical bone mass in mice with inactivation of interleukin‐4 and interleukin‐13

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 ¼ 7þ7), and WT (n ¼ 7þ7) 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 SOsteocalcin measurements. The skeletal phenotype was affected only in adult male IL-4mice. 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 À8.2%; femur À8.5%; 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 threepoint-bending at the mid-diaphyseal region of the femurs, demonstrated a significant reduction of displacement at failure (À11.4%), maximal load at failure (À10.6%), and total energy until failure (À29.4%). S-IGF-1 and S-Osteocalcin levels as well as trabecular bone mineral density (tvBMD) were unaffected in adult male IL-4IL-13 À/À 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. ß

Osteitis is a misnomer: a histopathology study in primary chronic rhinosinusitis

“…Neo‐osteogenesis, multiple sinus surgeries, and eosinophilic rhinosinusitis may share a common endpoint of recalcitrant disease secondary to poorly controlled inflammation. The concept of interleukin 4 (IL4) and IL13 playing an important role in the complex process of neo‐osteogenesis has been proposed in several studies . Neo‐osteogenesis may be merely an endpoint of a chronic process of T helper 2 (Th2) inflammation, driven by IL4 and IL13.…”

Cytokines TNF‐α, IL‐6, IL‐17F, and IL‐4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells

“…The T-helper 2 (Th2) cytokines IL-4, IL-10, and IL-13 belong to the family of anti-inflammatory cytokines that play an important role in inflammatory and immune responses [ 16 , 17 ]. In particular, IL-4 inhibits bone resorption [ 18 , 19 ], and its depletion can lead to a reduction in cortical bone mass in adult male mice [ 20 ]. In addition, IL-4 enhances osteogenesis by cocultures of proinflammatory M1 macrophages with preosteoblastic MC3T3 cells by modulating the M1 macrophage phenotype towards M2 [ 21 ].…”

Bone formation in interleukin‐4 and interleukin‐13 depleted mice

“…We found recently that there was a selective reduction of cortical bone mass in adult male mice depeleted of these Th2-related anti-inflammatory cytokines (Silfversward et al 2007). This finding prompted us to perform the present investigation, which was designed to investigate the role of IL-4 and IL-13 in bone formation.…”

“…In addition, excessive expression of IL-4 in transgenic mice results in a low-turnover osteoporosis (Lewis et al 1993). Recently, we found that depletion of IL-4 and IL-13 led to an isolated reduction in cortical bone mass in adult male mice (Silfversward et al 2007). As this indicates that IL-4 and IL-13 may possibly have a role in bone modeling, we considered that it would be of interest to study their effects in other events associated with bone formation, such as fracture healing and heterotopic bone formation.…”