Kuebart Till, Oezel Lisa, Gürsoy Beyza, Maus Uwe, Windolf Joachim, Bittersohl Bernd, Grotheer Vera
Department of Orthopedics and Trauma Surgery, Medical Faculty and University Hospital Duesseldorf, Heinrich Heine University, 40225 Duesseldorf, Germany.
Department of Orthopedics, Medical School and University Medical Center Ostwestalen-Lippe (OWL), Klinikum Bielefeld-Mitte, Bielefeld University, 33615 Bielefeld, Germany.
Int J Mol Sci. 2025 Jan 23;26(3):932. doi: 10.3390/ijms26030932.
Osteoporosis is an inflammatory disease characterised by low bone mass and quality, resulting in weaker bone strength and fragility fractures. Periostin is a matricellular protein expressed in the periosteum of bone by osteoblasts. It regulates cell recruitment and differentiation in response to fracture and contributes to extracellular matrix (ECM) formation. The aim of the following study was to determine the splice variants of Periostin expressed in human osteoblasts and Periostin's function in the pathophysiology of osteoporosis. Osteoblasts isolated from femoral heads from 29 patients with or without osteoporosis were utilised. Periostin splice variants were compared by quantitative real-time polymerase chain reaction (qPCR). Furthermore, the effect of Periostin inhibition on osteoblast differentiation was investigated using alizarin red S staining. Lastly, the interaction of IL-6 and Periostin and their effect on osteoprotegerin (OPG) secretion were analysed with the implantation of enzyme-linked immunosorbent assays (ELISAs). It could be demonstrated that human osteoblasts preferentially express Periostin isoform 4, even if splice variant expression was not altered in osteoporosis conditions, indicating that Periostin's functions in bone are primarily attributable to this isoform. The inhibition of Periostin resulted in significantly reduced osteoblast differentiation. However, Periostin was secreted in significantly higher amounts in osteoblasts from patients with osteoporosis. Additionally, Periostin significantly reduces OPG secretion and, thereby, rather promotes bone resorption. Furthermore, it could be determined that Periostin and IL-6 induce each other, and both significantly decrease OPG secretion. A positive feedback loop exacerbates the dysregulation found in human osteoblasts from patients with osteoporosis, thereby contributing to bone loss.
骨质疏松症是一种炎症性疾病，其特征是骨量和骨质量降低，导致骨强度减弱和脆性骨折。骨膜蛋白是一种基质细胞蛋白，由成骨细胞在骨膜中表达。它调节骨折后的细胞募集和分化，并有助于细胞外基质（ECM）的形成。以下研究的目的是确定人成骨细胞中表达的骨膜蛋白剪接变体以及骨膜蛋白在骨质疏松症病理生理学中的作用。利用从29例有或无骨质疏松症患者的股骨头中分离出的成骨细胞。通过定量实时聚合酶链反应（qPCR）比较骨膜蛋白剪接变体。此外，使用茜素红S染色研究骨膜蛋白抑制对成骨细胞分化的影响。最后，通过酶联免疫吸附测定（ELISA）植入分析白细胞介素-6（IL-6）与骨膜蛋白的相互作用及其对骨保护素（OPG）分泌的影响。结果表明，即使在骨质疏松症条件下剪接变体表达未改变，人成骨细胞也优先表达骨膜蛋白异构体4，这表明骨膜蛋白在骨中的功能主要归因于该异构体。骨膜蛋白的抑制导致成骨细胞分化显著降低。然而，骨质疏松症患者的成骨细胞中骨膜蛋白的分泌量显著更高。此外，骨膜蛋白显著降低OPG分泌，从而更促进骨吸收。此外，可以确定骨膜蛋白和IL-6相互诱导，并且两者均显著降低OPG分泌。正反馈回路加剧了骨质疏松症患者人成骨细胞中发现的失调，从而导致骨质流失。
