Transient and localized expression of bone morphogenetic protein 4 messenger RNA during fracture healing

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Abstract
Temporal and spatial distribution of a gene encoding murine bone morphogenetic protein 4 (mBMP‐4) during fracture repair were investigated in mice by RT‐PCR and in situ hybridization. For in situ hybridization, fractured ribs and surrounding tissues were decalcified and hybridized with a mBMP‐4‐specific complementary RNA probe labeled with digoxigenin‐11 UTP. mBMP‐4 messenger RNA (mRNA) was not detected in ribs without fracture, whereas it was detected only in the early phase of fracture from 12 to 72 h after the onset of fracture before new cartilage or bone formation. The mBMP‐4 mRNAs were present in cells distributed in three distinct regions, namely, the proliferating periosteum, the medullary cavity, and the muscles near the fracture site. These BMP‐4‐positive cells did not express bone gla protein mRNA, which is a marker of the mature osteogenic cell. RT‐PCR also showed a transient increase in the level of BMP‐4 mRNA in the early phase of fracture repair. The findings provide us with some new information. (1) The BMP‐4 gene is produced by less differentiated osteoprogenitor cells, not by differentiated osteoblasts. (2) The BMP‐4 gene is enhanced by the impact of fracture and localized in callus‐forming tissue before callus formation. Together with the activities of BMP‐4, as was previously described, our results suggest that newly produced BMP‐4 gene product is one of the local contributing factors in callus formation in the early phase of fracture healing.
Funding Information
  • the Japanese Ministry of Education (03404045)