Interleukin-11 acts synergistically with bone morphogenetic protein-2 to accelerate bone formation in a rat ectopic model.
We previously demonstrated that recombinant human interleukin-11 (rHuIL-11) induced osteoblast differentiation of C3H10T1/2 progenitor cells and also acted synergistically with recombinant human bone morphogenetic protein-2 (rHuBMP-2) in performing the same function. In this study, we investigated the effect of rHuIL-11 and rHuBMP-2 on bone formation in a rat ectopic model. When placed in rats, implants consisting of polymer-coated gelatin sponges containing various concentrations of rHuBMP-2 showed a dose-dependent increase in calcium content. This was confirmed by radiographic analysis of the implants. Although implants containing rHuIL-11 alone did not accumulate calcium, implants containing a combination of rHuBMP-2 and rHuIL-11 had significantly higher calcium levels than those containing rHuBMP-2 alone. This increase was rHuIL-11 dose dependent. The synergistic effect of 20 micrograms rHuIL-11 and 6 micrograms rHuBMP-2 on bone formation was estimated to be 1 week in advance of that of 6 micrograms rHuBMP-2 alone. Histologic examination revealed that the combination of rHuIL-11 and rHuBMP-2 caused spindle cells to accumulate around implants and induced cell infiltration into implants. Bone formation occurred faster in implants with the combination of rHuIL-11 and rHuBMP-2 compared with rHuBMP-2 alone. These results suggest that rHuIL-11 acts synergistically with rHuBMP-2 to more rapidly stimulate bone formation compared with rHuBMP-2 alone. This novel combined therapy may be of great clinical benefit in bone healing.
Suga
Kazutaka
K
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan. suga.kazutaka@yamanouchi.co.jp
Saitoh
Minori
M
Kokubo
Satoshi
S
Fukushima
Shinji
S
Kaku
Seiji
S
Yasuda
Shuhei
S
Miyata
Keiji
K
D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D001842:Bone and Bones; D002118:Calcium / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D019736:Prostheses and Implants; D051381:Rats; D020318:Rats, Long-Evans; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D017370:Interleukin-11; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D002118:Calcium