Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA.
Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Bone. 2021 Dec;153:116145. doi: 10.1016/j.bone.2021.116145. Epub 2021 Aug 12.
Metabolic bone is highly innervated by both sensory and sympathetic nerves. In addition to skeletal development, neural regulation participates in local bone remodeling, which is important for successful osseointegration of titanium implants. Neurectomy is a model used to investigate the lack of neural function on bone homeostasis, but the relative impacts of direct denervation to bone or denervation-induced muscle paralysis are less well defined. To investigate this difference, we used two nerve intervention models, sciatic and femoral neurectomy (SFN) v. botox-induced muscle paralysis (BTX) and assessed the resulting femoral bone phenotype and Ti implant osseointegration. Male Sprague Dawley rats (19) were randomly divided into three groups: implant control (n = 5), SFN (n = 7), and BTX (n = 7). Ti implants (microrough/hydrophilic [modSLA], Institut Straumann AG) were placed in the distal metaphysis of each femur on day 24 post-SFN or BTX. Bone and muscle were examined on day 28 after implant insertion. Both nerve intervention models impaired osseointegration. MicroCT and histology indicated that both models had reduced trabecular bone formation. Only BTX reduced cortical bone formation and increased cortical bone porosity. BTX resulted in more bone loss characterized by the least trabecular and cortical bone, as well as osseointegration. Osteoblasts isolated from the tibia exhibited a model-specific phenotype when they were grown on Ti substrates in vitro. Neurectomy caused more severe muscle atrophy than botox injection. These results indicate that neural regulation directly modulates bone formation and osseointegration. Muscle paralysis modulated the effects of loss of neural inputs into bone, supporting the hypothesis that mechanical loading of bone is a factor in achieving successful osseointegration. The different effects of botox and neurectomy on bone phenotype indicated that the sensory and sympathetic nerves had a role in the osseointegration process.
代谢性骨骼受到感觉神经和交感神经的双重支配。除了骨骼发育，神经调节还参与局部骨重塑，这对于钛植入物的成功骨整合非常重要。去神经支配是一种用于研究神经功能缺失对骨稳态影响的模型，但直接去神经支配对骨骼的影响或去神经支配引起的肌肉瘫痪的相对影响尚不清楚。为了研究这种差异，我们使用了两种神经干预模型，坐骨神经和股神经切除术（SFN）与肉毒杆菌毒素诱导的肌肉瘫痪（BTX），并评估了由此产生的股骨骨表型和 Ti 植入物骨整合。雄性 Sprague Dawley 大鼠（19 只）随机分为三组：植入物对照组（n=5）、SFN 组（n=7）和 BTX 组（n=7）。在 SFN 或 BTX 后第 24 天，将 Ti 植入物（微粗糙/亲水[modSLA]，Institut Straumann AG）放置在每只股骨的远端干骺端。在植入物插入后第 28 天检查骨和肌肉。两种神经干预模型均损害了骨整合。微 CT 和组织学表明，两种模型的小梁骨形成均减少。只有 BTX 减少了皮质骨形成并增加了皮质骨孔隙率。BTX 导致更多的骨丢失，其特征是最少的小梁骨和皮质骨以及骨整合。体外将从胫骨分离的成骨细胞种植在 Ti 基质上时，表现出特定于模型的表型。去神经支配引起的肌肉萎缩比肉毒杆菌毒素注射更严重。这些结果表明，神经调节直接调节骨形成和骨整合。肌肉瘫痪调节了失去神经输入到骨骼的影响，支持了骨骼机械加载是实现成功骨整合的一个因素的假说。肉毒杆菌毒素和去神经支配对骨骼表型的不同影响表明，感觉神经和交感神经在骨整合过程中起作用。
