Recombinant human bone morphogenetic protein-7 enhances fracture healing in an ischemic environment

Chuanyong Lu, Zhiqing Xing, Yan Yiu Yu, Celine Colnot, Theodore Miclau, Ralph S. Marcucio

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Ischemia predisposes orthopedic trauma patients to delayed fracture healing or nonunion. The goal of this study was to test the ability of bone morphogenetic protein 7 (BMP7) to stimulate fracture repair in an ischemic environment. Ischemic fractures were generated in male adult mice by resecting the femoral artery prior to the creation of a nonstabilized tibia fracture.Recombinant human BMP7(rhBMP7, 50 μg) was injected into the fracture site immediately after surgery. At 7 days after injury, more tissue vascularization was observed in rhBMP7 treated fractures. Histomorphometric analyses revealed that rhBMP7 induced more cartilage at day 7, more callus and bone at days 14 and 28, and more adipose tissue and fibrous tissue at days 7, 14, and 28 compared to controls (n=5/group/time). At day 28, all fractures treated with rhBMP7 (50 μg, n=5) healed, whereas only three of five control fractures exhibited slight bony bridging. In addition, we found that rhBMP7 (both 10 and 50 mg) significantly increased the amount of cartilage compared to controls in stabilized fractures, confirming its chondrogenic effect. Lastly, using bone marrow transplantation, we determined that no donor-derived osteocytes or chondrocytes were present in rhBMP7-treated fractures, suggesting rhBMP7 did not recruit mesenchymal stem cells from the bone marrow to the fracture site. In conclusion, our results indicate thatrhBMP7 is a promising treatment for fractures with severely disrupted blood supply.

Original languageEnglish (US)
Pages (from-to)687-696
Number of pages10
JournalJournal of Orthopaedic Research
Volume28
Issue number5
DOIs
StatePublished - May 1 2010
Externally publishedYes

Fingerprint

Fracture Healing
Cartilage
Bone Morphogenetic Protein 7
Osteocytes
Wounds and Injuries
Bony Callus
Femoral Artery
Chondrocytes
Tibia
Bone Marrow Transplantation
Mesenchymal Stromal Cells
Orthopedics
Adipose Tissue
Ischemia
Bone Marrow
Tissue Donors
Bone and Bones
human BMP7 protein
Therapeutics

Keywords

  • Bone morphogenetic protein 7
  • Fracture
  • Ischemia
  • Nonunion
  • Osteogenic protein-1

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Recombinant human bone morphogenetic protein-7 enhances fracture healing in an ischemic environment. / Lu, Chuanyong; Xing, Zhiqing; Yu, Yan Yiu; Colnot, Celine; Miclau, Theodore; Marcucio, Ralph S.

In: Journal of Orthopaedic Research, Vol. 28, No. 5, 01.05.2010, p. 687-696.

Research output: Contribution to journalArticle

Lu, Chuanyong ; Xing, Zhiqing ; Yu, Yan Yiu ; Colnot, Celine ; Miclau, Theodore ; Marcucio, Ralph S. / Recombinant human bone morphogenetic protein-7 enhances fracture healing in an ischemic environment. In: Journal of Orthopaedic Research. 2010 ; Vol. 28, No. 5. pp. 687-696.
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