title: Synergism between interleukin-11 and bone morphogenetic protein-2 in the healing of segmental bone defects in a rabbit model.
abstract: Recombinant human interleukin-11 (rHuIL-11) and recombinant human bone morphogenetic protein-2 (rHuBMP-2) have been shown to act synergistically in the induction of osteoblast differentiation. To determine whether these two proteins can be used clinically in fracture healing and reconstructive surgery, we investigated whether rHuIL-11 and rHuBMP-2 act synergistically to heal segmental bone defects in a rabbit model. A 1.5-cm segmental defect was created in the right ulnar diaphysis of 20 Japanese white rabbits. Polylactic-co-glycolic acid (PLGA)-coated gelatin sponges (PGS) permeated with rHuBMP-2 (n = 8), rHuIL-11 plus rHuBMP-2 (n = 8), or rHuIL-11 (n = 4) were implanted into the bone defects. Radiographs were scored by two independent observers for bone formation and union rates after 2, 3, 4, and 8 weeks. Bone formation was higher in rabbits implanted with rHuBMP-2 plus rHuIL-11 than in those implanted with rHuBMP-2 alone, reaching statistical significance after 4 weeks. At early time points, the union rate in rabbits implanted with rHuBMP-2 plus rHuIL-11 was higher than in rabbits implanted with rHuBMP-2. At 2, 4, and 8 weeks, new bone volume was significantly higher in rabbits administered rHuIL-11 plus rHuBMP-2 than in those given rHuBMP-2 alone. In contrast, mechanical testing after 8 weeks showed that bone strength in the two groups of rabbits was equivalent. These findings show that rHuIL-11 and rHuBMP-2 act synergistically to accelerate bone formation without affecting bone strength. Treatment with a combination of rHuIL-11 and rHuBMP-2 may thus be of great benefit in fracture healing and for patients undergoing reconstructive surgery.
authors.affiliation: Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., Tsukuba, Ibaraki, Japan. suga.kazutaka@yamanouchi.co.jp
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Suga
authors.forename: Minori
authors.initials: M
authors.lastname: Saitoh
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokubo
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Nozaki
authors.forename: Shinji
authors.initials: S
authors.lastname: Fukushima
authors.forename: Shuhei
authors.initials: S
authors.lastname: Yasuda
authors.forename: Masao
authors.initials: M
authors.lastname: Sasamata
authors.forename: Keiji
authors.initials: K
authors.lastname: Miyata
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D004337:Drug Carriers / Q000378:metabolism; D004357:Drug Synergism; D017102:Fracture Healing; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D011100:Polyglycolic Acid / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000378:metabolism; D011817:Rabbits; D011859:Radiography; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014457:Ulna / Q000000981:diagnostic imaging / Q000473:pathology
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D017370:Interleukin-11; D011108:Polymers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid