Department of Biosciences and Oral Diagnosis, São Paulo State University (Unesp), Institute of Science and Technology, São José dos Campos, São Paulo, Brazil.
Department of Molecular and Human Genetics and Orthopedic Surgery, Center for Skeletal Medicine and Biology, Baylor College of Medicine, Houston, TX, United States of America.
Life Sci. 2021 Sep 15;281:119776. doi: 10.1016/j.lfs.2021.119776. Epub 2021 Jun 27.
Stimulation of β-adrenergic receptors (βAR) in osteoblasts by isoproterenol (ISO) was shown to induce Vascular Endothelial Growth Factor (VEGF) and angiogenesis in long bones. We thus aimed to determine the vascular response of mandibular tissues to βAR stimulation regarding blood vessel formation.
Six-week-old wild-type C57BL6 female mice received daily intraperitoneal injections of ISO or phosphate buffered saline (PBS) for 1 month. Hemimandibles and tibias were collected for immunolocalization of endomucin, tyrosine hydroxylase (TH), neuropeptide Y (NPY) and norepinephrine transporter (NET). Moreover, Vegfa, Il-1 β, Il-6, Adrb2 and Rankl mRNA expression was assessed in mandibles and tibias 2 h after PBS or ISO treatment.
Despite similar sympathetic innervation and Adrb2 expression between mandibular tissues and tibias, with TH and NPY+ nerve fibers distributed around blood vessels, ISO treatment did not increase endomucin+ vessel area or the total number of endomucin+ vessels in any of the regions investigated (alveolar bone, periodontal ligament, and dental pulp). Consistent with these results, the expression of Vegfα, Il-6, Il-1β, and Rankl in the mandibular molar region did not change following ISO administration. We detected high expression of NET by immunofluorescence in mandible alveolar osteoblasts, osteocytes, and periodontal ligament fibroblasts, in addition to significantly higher Net expression by qPCR compared to the tibia from the same animals.
These findings indicate a differential response to βAR agonists between mandibular and tibial tissues, since the angiogenic potential of sympathetic outflow observed in long bones is absent in periodontal tissues.
异丙肾上腺素(ISO)对成骨细胞中β-肾上腺素能受体(βAR)的刺激被证明可诱导长骨中的血管内皮生长因子(VEGF)和血管生成。因此,我们旨在确定βAR 刺激下颌组织对血管形成的血管反应。
6 周龄野生型 C57BL6 雌性小鼠每天接受 ISO 或磷酸盐缓冲盐水(PBS)的腹腔内注射,持续 1 个月。收集半下颌骨和胫骨用于内皮黏蛋白、酪氨酸羟化酶(TH)、神经肽 Y(NPY)和去甲肾上腺素转运体(NET)的免疫定位。此外,在 PBS 或 ISO 处理后 2 小时评估下颌骨和胫骨中 Vegfa、Il-1β、Il-6、Adrb2 和 Rankl mRNA 的表达。
尽管下颌组织和胫骨之间具有相似的交感神经支配和 Adrb2 表达,并且 TH 和 NPY+神经纤维分布在血管周围,但 ISO 处理并未增加任何研究区域(牙槽骨、牙周韧带和牙髓)中内皮黏蛋白+血管面积或内皮黏蛋白+血管总数。与这些结果一致,ISO 给药后下颌磨牙区 Vegfα、Il-6、Il-1β 和 Rankl 的表达没有变化。我们通过免疫荧光检测到下颌牙槽骨成骨细胞、骨细胞和牙周韧带成纤维细胞中 NET 的高表达,并且与来自同一动物的胫骨相比,qPCR 检测到的 Net 表达明显更高。
这些发现表明下颌骨和胫骨组织对βAR 激动剂的反应不同,因为在长骨中观察到的交感神经流出的血管生成潜力在牙周组织中不存在。