Bone formation in interleukin-4 and interleukin-13 depleted mice.
OBJECTIVE
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.


CONCLUSIONS
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.
Silfverswärd
Carl-Johan
CJ
Department of Surgical Sciences, University of Uppsala, Uppsala, Sweden. carl-johan.silfversward@surgsci.uu.se
Sisask
Gregor
G
Larsson
Sune
S
Ohlsson
Claes
C
Frost
Anders
A
Ljunggren
Osten
O
Nilsson
Olle
O
D000818:Animals; D018775:Bone Demineralization Technique; D001857:Bone Matrix / Q000378:metabolism / Q000502:physiology; D016723:Bone Remodeling / Q000502:physiology; D002146:Bony Callus / Q000502:physiology; D005260:Female; D017102:Fracture Healing / Q000502:physiology; D050723:Fractures, Bone / Q000378:metabolism / Q000503:physiopathology; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009999:Ossification, Heterotopic; D010012:Osteogenesis / Q000502:physiology*
D018793:Interleukin-13; D015847:Interleukin-4