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Osteocyte TGF?1?Smad2/3 is positively associated with bone turnover parameters in subchondral bone of advanced osteoarthritis.

ABSTRACT: Subchondral sclerosis is considered the main characteristic of advanced osteoarthritis, in which bone remodeling mediated by transforming growth factor ? (TGF?) 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? 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? 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 osteoclastic activity in the cartilage and subchondral bone. The activation of the TGF? signaling pathway in the subchondral bone was detected by immunohistochemistry and western blotting. The association between osteocyte TGF? 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? 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? signaling could regulate the osteogenic and osteoclastic activity of the mesenchymal stem cells. This study illustrated that osteocyte TGF? 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? in subchondral of osteoarthritis.

SUBMITTER: Dai G

PROVIDER: S-EPMC7255453 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Osteocyte TGFβ1‑Smad2/3 is positively associated with bone turnover parameters in subchondral bone of advanced osteoarthritis.

Dai Guangming G Xiao Haozhuo H Liao Junyi J Zhou Nian N Zhao Chen C Xu Wei W Xu Wenjuan W Liang Xi X Huang Wei W

International journal of molecular medicine 20200414 1

Subchondral sclerosis is considered the main characteristic of advanced osteoarthritis, in which bone remodeling mediated by transforming growth factor β (TGFβ) 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 TGFβ signal and subchondral sclerosis. Knee tibia plateau sampl ...[more]

PMID: 32319543

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Project description:BackgroundSubchondral bone cysts are a widely observed, but poorly understood, feature in patients with knee osteoarthritis (OA). Clinical quantitative computed tomography (QCT) has the potential to characterize cysts in vivo but it is unclear which specific cyst parameters (e.g., number, size) are associated with clinical signs of OA, such as disease severity or pain. The objective of this study was to use QCT-based image-processing techniques to characterize subchondral tibial cysts in patients with knee OA and to explore relationships between proximal tibial subchondral cyst parameters and subchondral bone density as well as clinical characteristics of OA (alignment, joint space narrowing (JSN), OA severity, pain) in patients with knee OA.MethodsThe preoperative knee of 42 knee arthroplasty patients was scanned using QCT. Patient characteristics were obtained, including OA severity, knee pain, JSN, and alignment. We used 3D image processing techniques to obtain cyst parameters including: cyst number, cyst number per proximal tibial volume, cyst volume per proximal tibial volume, as well as maximum and average cyst volume across the proximal tibia, as well as regional bone mineral density (BMD) excluding cysts. We used Spearman's correlation coefficients to explore associations between patient characteristics and cyst parameters.ResultsAt both the medial and lateral compartments of the proximal tibia, greater cyst number and volume were associated with higher BMD. At the lateral region, cyst number and volume were also associated with lateral OA severity, lateral JSN, alignment and sex. Pain was not associated with any cyst parameters at any region.ConclusionCyst number and volume were associated with BMD at both the medial and lateral compartments. Lateral cyst number and volume were also associated with joint alignment, OA severity, JSN and sex. This is the first study to use clinical QCT to explore subchondral tibial cysts in patients with knee OA and provides further evidence of the relationships between subchondral cysts and clinical OA characteristics.

Dataset Information

Osteocyte TGF?1?Smad2/3 is positively associated with bone turnover parameters in subchondral bone of advanced osteoarthritis.

Publications

Osteocyte TGFβ1‑Smad2/3 is positively associated with bone turnover parameters in subchondral bone of advanced osteoarthritis.

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