Bone formation zones in heterotopic ossifications : histologic findings and increased expression of bone morphogenetic protein 2 and transforming growth factors beta2 and beta3

• Heterotopic ossifications (HOs) formed after total endoprosthetic replacement of the hip joint were collected during revision surgery (n = 7). Tissues collected during regular hip arthroplasty (n = 12) were used as reference. Histomorphometric analysis was performed for assessment of bone formation activity in HOs and reference bone. HOs were dissected with histological guidance into three zones: formed bone, zone of active bone formation, and zone with fibrous connective and fibrocartilagineous tissue. Relative expression of the mRNA for bone morphogenetic protein 2 (BMP-2), transforming growth factor beta2 (TGF-beta2), and TGF-beta3 was determined by reverse-transcription polymerase chain reaction relative to beta-actin. Expression of all three growth factors was higher than in orthotopic bone. Similarly, the osteoid surface density was increased in HOs. The levels of all growth factors were higher in the zone of active bone formation or remodeling than in the zone of formed bone. In matured HOs, the osteoid surface density as well as mRNA levels were lower, although still significantly raised, indicating that bone formation slows down after 2 years. Immunohistochemical analysis demonstrated the presence of TGF-beta1, TGF-beta2, TGF-beta3, and BMP-2 proteins in the zone of bone formation. We conclude that bone formation after heterotopic bone induction is initially intense, slows down within 2 years, and thereupon continues as active remodeling mainly on the border of HO. Our data indicate that BMP-2, TGF-beta2, and TGF-beta3 are involved in bone formation in HO.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Bone Morphogenetic Proteins/*genetics/metabolism

Case-Control Studies

Female

Gene Expression Regulation

Humans

Immunohistochemistry

Male

Middle Aged

Ossification; Heterotopic/*genetics/metabolism/*pathology

Osteogenesis/genetics/*physiology

RNA; Messenger/metabolism

Transforming Growth Factor beta/*genetics/metabolism

Transforming Growth Factor beta2/*genetics/metabolism

Transforming Growth Factor beta3/*genetics/metabolism

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