Department of Orthopaedics and Traumatology, Faculty of Medical Sciences, The State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Clin Orthop Relat Res. 2010 Apr;468(4):1149-56. doi: 10.1007/s11999-009-1146-6. Epub 2009 Oct 23.
Low-intensity pulsed ultrasound stimulation (LIPUS) reportedly increases osteogenesis in fracture models but fails in intact bone, suggesting LIPUS does not act on mechanotransduction and growth factor pathways of intact bone.
QUESTIONS/PURPOSES: We asked whether daily 20-minute LIPUS applied to intact tibias would act on bone proteins involved in mechanotransduction (focal adhesion kinase [FAK], and extracellular signal-regulated kinase-1/2 [ERK-1/2]), and growth factor signaling (insulin receptor substrate-1 [IRS-1]) pathways at 7, 14, and 21 days of treatment.
Immunoblotting was performed to detect FAK, ERK-1/2, and IRS-1 expression and activation from the stimulated intact tibias at 7, 14, and 21 days of daily 20-minute LIPUS.
LIPUS increased FAK expression (at 7 days), ERK-1/2 (at 14 days), and IRS-1 (at 7 days), but expression decreased 7 days later, indicating a noncumulative effect of LIPUS. As only FAK expression was detected at 21 days, these observations suggest LIPUS influences nuclear reactions that may be modulated by a major cellular mechanism preferentially inhibiting IRS-1 expression and not FAK expression. Increased ERK-1/2 expression at 14 days suggests the differing mechanisms for promoting ERK-1/2, FAK, and IRS-1 syntheses. IRS-1 expression behaved similarly to FAK expression; therefore, LIPUS may modulate growth factor pathways. LIPUS increased sustained FAK and ERK-1/2 activation, but not IRS-1, suggesting sustained ERK-1/2 activation is not the result of mechanically induced growth factor activation.
LIPUS acts on mechanotransduction and growth factor pathways in intact bone in a noncumulative manner. Clinical relevance These data suggest LIPUS applied to intact bone acts on proteins involved in osteogenesis.
低强度脉冲超声刺激（LIPUS）据称可增加骨折模型中的成骨作用，但在完整骨中无效，这表明 LIPUS 不会作用于完整骨的机械转导和生长因子途径。
问题/目的：我们想知道，每天 20 分钟的 LIPUS 应用于完整的胫骨是否会作用于机械转导（粘着斑激酶[FAK]和细胞外信号调节激酶-1/2[ERK-1/2]）和生长因子信号（胰岛素受体底物-1[IRS-1]）途径中的骨蛋白在治疗的第 7、14 和 21 天。
使用免疫印迹法检测刺激后的完整胫骨中 FAK、ERK-1/2 和 IRS-1 的表达和激活在第 7、14 和 21 天接受每日 20 分钟 LIPUS。
LIPUS 增加了 FAK 的表达（第 7 天），ERK-1/2（第 14 天）和 IRS-1（第 7 天），但 7 天后表达减少，表明 LIPUS 的作用是非累积的。由于仅在第 21 天检测到 FAK 表达，这些观察结果表明 LIPUS 影响了核反应，这些反应可能受一种主要的细胞机制调节，该机制优先抑制 IRS-1 表达而不是 FAK 表达。14 天 ERK-1/2 表达增加表明促进 ERK-1/2、FAK 和 IRS-1 合成的不同机制。IRS-1 的表达与 FAK 的表达相似；因此，LIPUS 可能调节生长因子途径。LIPUS 增加了持续的 FAK 和 ERK-1/2 的激活，但 IRS-1 没有增加，这表明持续的 ERK-1/2 激活不是机械诱导生长因子激活的结果。
LIPUS 以非累积的方式作用于完整骨中的机械转导和生长因子途径。临床意义这些数据表明，应用于完整骨的 LIPUS 作用于涉及成骨的蛋白质。
