The Expression of Osteogenic Factors in Low-Intensity Pulsed Ultrasound-Enhanced Healing of Femoral Nonunion in Rats

Low-intensity pulsed ultrasound (US) is noninvasive acoustic wave, which has been demonstrated to promoted fracture healing. The actual healing mechanism triggered by US has not been identified. Bone morgenetic protein-2 (BMP-2), transforming growth factor-β1 (TGF-β1), insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) have been implicated as playing an important role in bone development and fracture healing. Systemic increases in osteogenic factors reflect a local stimulation of bone formation. In this study, we aimed to examine whether physical US stimulated induction of BMP-2, TGF-β1, IGF-I and bFGF during healing of nonunion. Rats with femoral nonunion were given 4 sessions of US treatment (200μs pulse burst width, 1kHz, 30mW/cm^2) for 20 min. Blood was harvested via intracardic needle and processed to collect serum 1, 2, 4, 6 weeks following US treatment. BMP-2, TGF-β1, IGF-I, bFGF, osteoclacin levels and bone alkaline phosphatase in serum were determined using specific rat ELISA kits. Local osteogenic factor expression in calluses was assayed by immuonhistochemistry. Results showed that nonunion subjected to US treatment significantly increased systemic BMP-2 production in 1 week, peaking at 2 weeks and following by decline to baseline 4 weeks after treatment. US treatment significantly increases circulating IGF-I level and bFGF in 2 weeks and persisted to 6 weeks. There was no significant alteration of TGF-β1 levels between US-treated and control groups. Increases in osteogenic factor levels associated with up-regulation of serum bone alkaline phosphatase activity and osteocalcin level. Systemic ostegenic regulation was coincidence with intense osteogenesis and chondrogenesis in calluses after US treatment. Our findings indicated that nonunion responds to US treatment by elevating bone forming activities. Ultrasound treatment is an alternative biophysical strategy for bone repair. BMP-2, bFGF and IGF-I are probably active in US promotion of healing of nonunion. Systemic increases in osteogenic factors reflect a local stimulation of bone formation. Increases in serum BMP-2, bFGF and IGF-I levels also provide useful biochemical method to elucidate the clinical effectiveness of US application on fracture healing.

並列關鍵字

nonunion ； BMP-2 ； IGF-I ； PCNA ； low-intensity pulsed ultrasound

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