Adipose-Derived Mesenchymal Stem Cells-Conditioned Medium Modulates the Expression of Inflammation Induced Bone Morphogenetic Protein-2, -5 and -6 as Well as Compared with Shockwave Therapy on Rat Knee Osteoarthritis.

Jai-Hong Cheng,Wen-Yi Chou,Shan-Ling Hsu,Li-Yen Shiu,Tsai-Chin Hsu,Chun-En Aurea Kuo,Chieh-Cheng Hsu,Yi-No Wu,Shun-Wun Jhan

doi:10.3390/biomedicines9101399

Abstract

The dose-dependent effects of adipose-derived mesenchymal stem cell-conditioned medium (ADSC-CM) were compared with those of shockwave (SW) therapy in the treatment of early osteoarthritis (OA). Anterior cruciate ligament transaction (ACLT) with medial meniscectomy (MMx) was performed in rats divided into sham, OA, SW, CM1 (intra-articular injection of 100 μL ADSC-CM into knee OA), and CM2 (intra-articular injection of 200 μL ADSC-CM) groups. Cartilage grading, grading of synovium changes, and specific molecular analysis by immunohistochemistry staining were performed. The OARSI and synovitis scores of CM2 and SW group were significantly decreased compared with those of the OA group (p < 0.05). The inflammatory markers interleukin 1β, terminal deoxynucleotidyl transferase dUTP nick end labeling and matrix metalloproteinase 13 were significantly reduced in the CM2 group compared to those in the SW and CM1 groups (p < 0.001). Cartilage repair markers (type II collagen and SRY-box transcription factor 9, SOX9) expression were significantly higher in the CM2 group than in the other treatment groups (p < 0.001; p < 0.05). Furthermore, inflammation-induced growth factors such as bone morphogenetic protein 2 (BMP2), BMP5, and BMP6 were significantly reduced in the treatment groups, and the CM2 group showed the best results among the treatments (p < 0.05). In conclusion, ADSC-CM and SW ameliorated the expression of inflammatory cytokines and inflammation-induced BMPs to protect the articular cartilage of the OA joint.

Highlights

Osteoarthritis (OA) is a degenerative joint disease that results in damage to the cartilage and subchondral bone and has a significant impact on health care [1]
The results demonstrated that the expression of inflammatory cytokines (IL1-β), apoptosis activity (TUNEL), and markers for OA (MMP13) were induced in knee OA, and were reduced after adipose-derived mesenchymal stem cell-conditioned medium (ADSC-conditioned medium (CM)) and SW therapy
Rat Adipose-tissue-derived mesenchymal stem cells (ADSCs)-CM and SW therapy can protect against the loss of extracellular matrix in the articular cartilage and improve synovitis in knee OA

Summary

Introduction

Osteoarthritis (OA) is a degenerative joint disease that results in damage to the cartilage and subchondral bone and has a significant impact on health care [1]. Many factors can be characterized for OA, such as synovitis, joint space narrowing, degeneration of articular cartilage and meniscus, subchondral bone remodeling, inflammation of the infrapatellar fat pad, and fibrosis [2,3]. The expression of proinflammatory cytokines including interleukin 1β (IL1β) and tumor necrosis factor α (TNFα) is important in the swollen synovium in OA. These key factors are accompanied by the increased expression of cytokine receptors and reduced expression of inhibitory proteins. These cytokines correlate with cartilage damage by the up regulation of inflammatory or catabolic genes as well as the down regulation of anti-inflammatory or anabolic genes in articular cartilage [4,5]. The inflammation induced by BMPs and cytokines of the joint causes a dysregulated expression of catabolic (cartilaginous matrix proteins) and anabolic proteins (MMPs) to destabilized cartilage homeostasis [10,11]

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