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Osteocyte TGFβ1-Smad2/3 is positively associated with bone turnover parameters in subchondral bone of advanced osteoarthritis
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DOI：10.3892/ijmm.2020.4576.png)
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Abstract
En 中文
Subchondral sclerosis is considered the main characteristic of advanced osteoarthritis, in which bone remodeling mediated by transforming growth factor beta (TGF beta) signaling plays an indispensable role in the metabolism. Osteocytes have been identified as pivotal regulators of bone metabolism, due to their mechanosensing and endocrine function. Therefore, the aim of the present study was to investigate the association between osteocyte TGF beta signal and subchondral sclerosis. Knee tibia plateau samples were collected from osteoarthritic patients and divided into three groups: The full cartilage, partial cartilage and full defect groups. Next, changes in osteocyte TGF beta signaling and subchondral bone structure underlying various types of cartilage erosion were detected. Bone mineral density (BMD) assay, histology [hematoxylin and eosin, Safranin-O/Fast green, and tartrate resistant acid phosphatase (TRAP) staining], and reverse transcription-quantitative PCR mainly detected structural alterations, osteogenic and osteo-clastic activity in the cartilage and subchondral bone. The activation of the TGF beta signaling pathway in the subchondral bone was detected by immunohistochemistry and western blotting. The association between osteocyte TGF beta and the regulation of bone metabolism was analyzed by correlation analysis, and further proven in vitro. It was confirmed that the BMD of the subchondral bone increased and underwent sclerosis in the partial cartilage and full defect groups. Additional observation included the thinning of the area of calcified cartilage, in which a bone island formed locally, with subchondral bone plate thickening and increased trabecular bone volume. TRAP staining suggested an increase in bone resorption in subchondral underlying areas of the partial cartilage and full defect groups. Immunohistochemistry results confirmed the activation of osteocyte TGF beta in subchondral underlying areas with severe cartilage erosion. Moreover, osteocyte phosphorylated-Smad2/3 was positively correlated with subchondral BMD, alkaline phosphatase and osteopontin mRNA expression, but it was negatively correlated with TRAP(+) cells. Furthermore, it was confirmed in vitro that osteocyte TGF beta signaling could regulate the osteogenic and osteoclastic activity of the mesenchymal stem cells. This study illustrated that osteocyte TGF beta signaling is positively associated with the remodeling of subchondral bone in advanced osteoarthritis and provides a preliminary theoretical basis for further investigations of the role and mechanism of osteocyte TGF beta in subchondral of osteoarthritis.
Keywords:
transforming growth factor beta
osteocytes
osteoarthritis
subchondral bone
sclerosis
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