Department of MedicineInternal Medicine, Section D, University of Verona, Verona, Italy.
Department of NeurosciencesBiomedicine and Movement Sciences, University of Verona, Verona, Italy
Endocr Relat Cancer. 2018 Mar;25(3):269-277. doi: 10.1530/ERC-17-0523. Epub 2018 Jan 2.
Acromegalic patients, characterized by excessive secretion of GH and IGF-1, show a high fracture risk but bone mineral density is a poor predictor for bone fractures in these patients. The effects of an excess of GH/IGF1 on skeleton as well as on osteogenic progenitors, i.e. mesenchymal stem cells, have not been investigated in these patients. We aimed to elucidate the skeletal conditions of acromegalic patients by means of bone microarchitecture analysis and evaluation of MSCs osteogenic commitment. In particular, we performed histomorphometric analyses, and we quantified the expression levels of the osteogenic transcription factor RUNX2 in circulating MSCs. Our results showed an abnormal microarchitecture and demonstrated that bone impairment in acromegalic patients is associated with the upregulation of expression. Furthermore, osteoblastic activity was significantly reduced in patients under pharmacological treatment, compared to untreated patients. In conclusion, this study demonstrates the key role of gene overexpression in causing bone impairment in acromegalic patients. It also suggests a therapeutic approach for the improvement of bone quality, focused on the osteoblastic lineage rather than the inhibition of osteoclastic activity.
肢端肥大症患者的特点是生长激素（GH）和胰岛素样生长因子 1（IGF-1）过度分泌，骨折风险较高，但骨密度是这些患者发生骨折的不良预测指标。GH/IGF1 对骨骼以及成骨祖细胞（即间充质干细胞）的影响在这些患者中尚未得到研究。我们旨在通过骨微结构分析和间充质干细胞成骨分化能力的评估来阐明肢端肥大症患者的骨骼状况。具体而言，我们进行了组织形态计量学分析，并检测了循环间充质干细胞中成骨转录因子 RUNX2 的表达水平。我们的结果显示出异常的微结构，并表明骨损伤与表达上调有关。此外，与未接受治疗的患者相比，接受药物治疗的患者的成骨细胞活性明显降低。总之，这项研究表明基因过度表达在肢端肥大症患者骨损伤中的关键作用。它还提示了一种针对改善骨质量的治疗方法，重点关注成骨细胞谱系，而不是抑制破骨细胞活性。
