Mechanical stimulation alters tissue differentiation and molecular expression during bone healing.

Mechanical stimulation alters tissue differentiation and molecular expression during bone healing.
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DOI:
10.1002/jor.20863
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发表时间:
2009-09
影响因子:
2.8
通讯作者:
Morgan, Elise F.
Morgan, Elise F.
中科院分区:
医学3区
文献类型:
--
作者:
Palomares, Kristy T. Salisbury;Gleason, Ryan E.;Mason, Zachary D.;Cullinane, Dennis M.;Einhorn, Thomas A.;Gerstenfeld, Louis C.;Morgan, Elise F.

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进一步了解机械信号如何调节骨骼组织分化可以确定增强损伤或疾病后修复的潜在方法。先前的研究检查了机械负荷对成骨、软骨生成和纤维生成的影响,以增强骨结合。然而,探索机械刺激如何将骨愈合过程转向其他间质组织的形成作为终点,可能会阐明软骨和纤维组织等组织修复和再生的新途径。这项研究调查了在截骨术中使用机械刺激来促进软骨而不是骨形成。我们的总体目标是定义刺激诱导的骨骼组织分布和分子表达模式。退役饲养 Sprague-Dawley 大鼠(n = 85)接受了中骨干横向股骨截骨术,然后进行外固定。从术后第 10 天开始,持续 1、2 或 4 周,在矢状面进行循环弯曲运动(+35°/−25°,1Hz),每天 15 分钟,连续五天/周。对照动物经历持续的刚性固定。组织学和分子分析表明,刺激显着改变了正常的骨愈合。随着时间的推移,受刺激的标本表现出软骨体积的增加,而对照标本则表现出骨桥。刺激诱导软骨相关基因(COL2A1 和 COL10A1)上调以及骨形态发生蛋白(BMP)-4、-6 和 -7 下调。然而,BMP-3 随刺激而上调。这些发现表明,机械信号可以选择性地调节体内成骨和软骨生成,并为受伤或患病软骨组织的治疗方案提供了潜在的基础。
Further understanding of how mechanical cues modulate skeletal tissue differentiation can identify potential means of enhancing repair following injury or disease. Prior studies examined the effects of mechanical loading on osteogenesis, chondrogenesis, and fibrogenesis in an effort to enhance bony union. However, exploring how mechanical stimuli can divert the bone healing process towards formation of other mesenchymal tissues as an endpoint may elucidate new avenues for repair and regeneration of tissues such as cartilage and fibrous tissue. This study investigated the use of mechanical stimulation to promote cartilage rather than bone formation within an osteotomy. Our overall goal was to define skeletal tissue distribution and molecular expression patterns induced by the stimulation. Retired breeder Sprague-Dawley rats (n=85) underwent production of a mid-diaphyseal, transverse femoral osteotomy followed by external fixation. Beginning on post-operative day 10 and continuing for 1, 2, or 4 weeks, a cyclic bending motion (+35°/−25° at 1Hz) was applied in the sagittal plane for 15 minutes/day for five consecutive days/week. Control animals experienced continuous rigid fixation. Histological and molecular analyses indicated that stimulation substantially altered normal bone healing. Stimulated specimens exhibited an increase in cartilage volume over time, while control specimens demonstrated bony bridging. Stimulation induced upregulation of cartilage-related genes (COL2A1 and COL10A1) and downregulation of bone morphogenetic proteins (BMPs) −4, −6 and −7. However, BMP-3 was upregulated with stimulation. These findings illustrate that mechanical cues can selectively modulate osteogenesis and chondrogenesis in vivo, and suggest a potential basis for treatment regimens for injured or diseased cartilaginous tissues.
DOI: 10.1097/00005131-200101000-00010
发表时间: 2001-01-01
影响因子: 2.3
作者:
Augat, P;Merk, J;Claes, L
通讯作者: Claes, L
DOI: 10.1242/jeb.00453
发表时间: 2003-07-01
影响因子: 2.8
作者:
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发表时间: 1998-07-01
影响因子: 2.8
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发表时间: 1999-03-01
影响因子: 2.4
作者:
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DOI: 10.1080/000164700317362172
发表时间: 2000-12-01
期刊: ACTA ORTHOPAEDICA SCANDINAVICA
影响因子: --
作者:
Aspenberg, P;Basic, N;Vukicevic, S
通讯作者: Vukicevic, S