PMID- 15212708 OWN - NLM STAT- MEDLINE DCOM- 20050329 LR - 20181130 IS - 1079-9907 (Print) IS - 1079-9907 (Linking) VI - 24 IP - 6 DP - 2004 Jun TI - Synergism between interleukin-11 and bone morphogenetic protein-2 in the healing of segmental bone defects in a rabbit model. PG - 343-9 AB - 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. FAU - Suga, Kazutaka AU - Suga K AD - Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., Tsukuba, Ibaraki, Japan. suga.kazutaka@yamanouchi.co.jp FAU - Saitoh, Minori AU - Saitoh M FAU - Kokubo, Satoshi AU - Kokubo S FAU - Nozaki, Kazutoshi AU - Nozaki K FAU - Fukushima, Shinji AU - Fukushima S FAU - Yasuda, Shuhei AU - Yasuda S FAU - Sasamata, Masao AU - Sasamata M FAU - Miyata, Keiji AU - Miyata K LA - eng PT - Journal Article PL - United States TA - J Interferon Cytokine Res JT - Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research JID - 9507088 RN - 0 (BMP2 protein, human) RN - 0 (Biocompatible Materials) RN - 0 (Bone Morphogenetic Protein 2) RN - 0 (Bone Morphogenetic Proteins) RN - 0 (Drug Carriers) RN - 0 (Interleukin-11) RN - 0 (Polymers) RN - 0 (Recombinant Proteins) RN - 0 (Transforming Growth Factor beta) RN - 0 (recombinant human bone morphogenetic protein-2) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 26009-03-0 (Polyglycolic Acid) RN - 33X04XA5AT (Lactic Acid) SB - IM MH - Animals MH - Biocompatible Materials/metabolism MH - Bone Morphogenetic Protein 2 MH - Bone Morphogenetic Proteins/*pharmacology MH - Bone Regeneration/*drug effects/physiology MH - Drug Carriers/metabolism MH - *Drug Synergism MH - *Fracture Healing MH - Humans MH - Interleukin-11/*pharmacology MH - Lactic Acid/metabolism MH - Male MH - Polyglycolic Acid/metabolism MH - Polylactic Acid-Polyglycolic Acid Copolymer MH - Polymers/metabolism MH - Rabbits MH - Radiography MH - Recombinant Proteins MH - Transforming Growth Factor beta/*pharmacology MH - Ulna/diagnostic imaging/pathology EDAT- 2004/06/24 05:00 MHDA- 2005/03/30 09:00 CRDT- 2004/06/24 05:00 PHST- 2004/06/24 05:00 [pubmed] PHST- 2005/03/30 09:00 [medline] PHST- 2004/06/24 05:00 [entrez] AID - 10.1089/107999004323142204 [doi] PST - ppublish SO - J Interferon Cytokine Res. 2004 Jun;24(6):343-9. doi: 10.1089/107999004323142204.