Department of Plastic Surgery, BG University Hospital Bergmannsheil, 44789 Bochum, Germany.
Department for Orthodontics, University Hospital Düsseldorf, 40225 Dusseldorf, Germany.
Cells. 2022 Feb 10;11(4):612. doi: 10.3390/cells11040612.
Diabetes mellitus has multiple negative effects on regenerative processes, especially on wound and fracture healing. Despite the well-known negative effects of diabetes on the autonomous nervous system, only little is known about the role in bone regeneration within this context. Subsequently, we investigated diabetic bone regeneration in db/db mice with a special emphasis on the sympathetic nervous system of the bone in a monocortical tibia defect model. Moreover, the effect of pharmacological sympathectomy via administration of 6-OHDA was evaluated in C57Bl6 wildtype mice. Diabetic animals as well as wildtype mice received a treatment of BRL37344, a β3-adrenergic agonist. Bones of animals were examined via µCT, aniline-blue and Masson-Goldner staining for new bone formation, TRAP staining for bone turnover and immunoflourescence staining against tyrosinhydroxylase and stromal cell-derived factor 1 (SDF-1). Sympathectomized wildtype mice showed a significantly decreased bone regeneration, just comparable to db/db mice. New bone formation of BRL37344 treated db/db and sympathectomized wildtype mice was markedly improved in histology and µCT. Immunoflourescence stainings revealed significantly increased SDF-1 due to BRL37344 treatment in diabetic animals and sympathectomized wildtypes. This study depicts the important role of the sympathetic nervous system for bone regenerative processes using the clinical example of diabetes mellitus type 2. In order to improve and gain further insights into diabetic fracture healing, β3-agonist BRL37344 proved to be a potent treatment option, restoring impaired diabetic bone regeneration.
糖尿病对再生过程有多种负面影响，尤其是对伤口和骨折愈合。尽管众所周知糖尿病对自主神经系统有负面影响，但在这方面，对骨骼再生的作用知之甚少。随后，我们在 db/db 小鼠的单皮质胫骨缺损模型中研究了糖尿病对骨骼再生的影响，特别强调了骨骼中的交感神经系统。此外，还通过给予 6-OHDA 评估了药物性交感神经切除术对 C57Bl6 野生型小鼠的影响。糖尿病动物和野生型小鼠均接受了 BRL37344（β3-肾上腺素能激动剂）的治疗。通过 µCT、苯胺蓝和 Masson-Goldner 染色评估新骨形成、TRAP 染色评估骨转换以及针对酪氨酸羟化酶和基质细胞衍生因子 1（SDF-1）的免疫荧光染色来检查动物的骨骼。交感神经切除术的野生型小鼠的骨再生明显减少，与 db/db 小鼠相当。BRL37344 治疗的 db/db 和交感神经切除术的野生型小鼠的新骨形成在组织学和 µCT 上明显改善。免疫荧光染色显示，由于糖尿病动物和交感神经切除术的野生型小鼠中 BRL37344 的治疗，SDF-1 明显增加。这项研究使用 2 型糖尿病的临床实例描绘了交感神经系统对骨骼再生过程的重要作用。为了改善和进一步了解糖尿病骨折愈合，β3-激动剂 BRL37344 被证明是一种有效的治疗选择，可以恢复受损的糖尿病骨骼再生。
