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Molecular signaling in bone fracture healing and distraction
osteogenesis
Z. Liu1,2, F.P. Luyten1, J. Lammens2 and J.
Dequeker1
Departments of 1Rheumatology and 2Orthopaedic
Surgery, U. Z. Leuven, Pellenberg, Belgium
Offprint requests to: Dr.
Z. Liu, Laboratory for Skeletal Development and Joint Disorders,
U.Z. Gasthuisberg, B-3000, Leuven, Belgium. Fax: 032-16-346200
Summary. The
process of fracture healing has been described in detail in many
histological studies. Recent work has focused on the mechanisms
by which growth and differentiation factors regulate the fracture
healing process. Rapid progress in skeletal cellular and molecular
biology has led to the identification of many signaling molecules
associated with the formation of skeletal tissues, including members
of the transforming growth factor-ß (TGF-ß) superfamily
and the insulin-like growth factor (IGF) family. Increasing evidence
indicates that they are critical regulators of cellular proliferation,
differentiation, extracellular matrix biosynthesis and mineralization.
Limb lengthening procedure (distraction osteogenesis) is a relevant
model to investigate the in vivo correlation between mechanical
stimulation and biological responses as the callus is stretched
by a proper rate and rhythm of mechanical strain. This model also
provides additional insights into the molecular and cellular events
during bone fracture repair. TGF-ß1 was significantly increased
in both the distracted callus and the fracture callus. The increased
level of TGF-ß1, together with a low concentration of calcium
and an enhanced level of collagen synthesis, was maintained in
the distracted callus as long as mechanical strain was applied.
Less mineralization is also associated with a low level of osteocalcin
production. These observations provide further insights into the
molecular basis for the cellular events during distraction osteogenesis.
Histol. Histopathol. 14, 587-595 (1999)
Key words: Growth
factors, fracture healing, Distraction osteogenesis, Mechanical
strain
DOI: 10.14670/HH-14.587
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