Bone formation in interleukin-4 and interleukin-13 depleted mice
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Carl-Johan Silfverswärd1, Gregor Sisask, Sune Larsson
1Department of Surgical Sciences, University of Uppsala, Uppsala, Sweden. carl-johan.silfversward@surgsci.uu.se
Background And Purpose:
Cytokines play an important role in the complex process of bone formation. We have previously found an altered skeletal phenotype with reduction of cortical bone mass in mice depleted of the 2 cytokines interleukin-4 (IL-4) and interleukin-13 (IL 13). The present study was performed to investigate a potential role of IL-4 and IL-13 in fracture healing and bone induction by demineralized xenogenic bone matrix (DXBM).
Methods:
Callus formation in IL-4-(/)-IL-13-(/)- (IL-4/13 knockout) and wild-type (WT) male mice was compared using a standardized fracture model. The capacity of IL-4(-/-)IL-13(-/-) and WT male and female mice to form heterotopic bone was compared using intramuscular implants of DXBM. Bone formation and mechanical properties were evaluated by pQCT, ash weight, 3-point bending, radiology, and immunohistology.
Results:
In the fracture investigation substantial amounts of new bone formation by 5 weeks were found, but no differences in radiographical healing, callus volume, BMD, BMC, or mechanical properties were detected between IL-4(-/-)IL-13(-/-) and WT mice. In the DXBM investigation radiographic analysis confirmed mineralization of implants in both groups, but no difference in the amount of mineral deposition (net bone formation) between IL-4(-/-)IL-13(-/-) and WT mice was found. Immunohistology showed inhibition of autonomic nerves in the capsule of the IL-4(-/-)IL-13(-/-) group along with a lack of vascularization within the implants.
Interpretation:
Depletion of IL-4 and IL-13 does not cause any major alteration in fracture healing or heterotopic bone formation in mice. The pattern of autonomous nerve expression and expression of markers of neovascularization is, however, altered to some extent by the absence of IL-4 and IL-13.
Insights
Depletion of interleukin-4 (IL-4) and interleukin-13 (IL-13) does not significantly impact mouse fracture healing or bone induction. However, nerve and vascularization patterns are altered in their absence.
Area of Science:
- Immunology
- Orthopedics
- Regenerative Medicine
Background:
- Cytokines, including interleukin-4 (IL-4) and interleukin-13 (IL-13), are crucial in bone formation.
- Previous studies indicated that IL-4 and IL-13 depletion alters skeletal phenotype and reduces cortical bone mass.
- The role of IL-4 and IL-13 in fracture healing and bone induction requires further investigation.
Purpose of the Study:
- To investigate the role of IL-4 and IL-13 in fracture healing in mice.
- To assess the impact of IL-4 and IL-13 depletion on bone induction by demineralized xenogenic bone matrix (DXBM).
Main Methods:
- Fracture healing was compared between IL-4/IL-13 knockout and wild-type (WT) mice using a standardized fracture model.
- Bone formation capacity was evaluated using intramuscular DXBM implants in knockout and WT mice.
- Bone formation, mineralization, and mechanical properties were assessed via pQCT, ash weight, 3-point bending, radiology, and immunohistology.
Main Results:
- No significant differences in fracture healing, callus volume, bone mineral density (BMD), bone mineral content (BMC), or mechanical properties were observed between knockout and WT mice.
- Radiographic analysis showed similar mineralization of DXBM implants, with no difference in net bone formation between groups.
- Immunohistology revealed inhibited autonomic nerve presence and reduced vascularization within implants in the knockout group.
Conclusions:
- Absence of IL-4 and IL-13 does not substantially affect fracture healing or heterotopic bone formation in mice.
- The study identified alterations in autonomous nerve expression and neovascularization markers in IL-4 and IL-13 deficient mice.
- These findings suggest a nuanced role for IL-4 and IL-13 in the microenvironment of bone healing and regeneration.
