Low-intensity pulsed ultrasound inhibits VEGFA expression in chondrocytes and protects against cartilage degeneration in experimental osteoarthritis.

Huabing Qi,Bo Liao,Dingqun Bai,Mengtong Guan,Bin Zhang,Ying Zhu,Junlan Huang,Xiaolan Du,Qiaoyan Tan

doi:10.1002/2211-5463.12801

Abstract

Low‐intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, was recently demonstrated to be an effective treatment for osteoarthritis (OA). Vascular endothelium growth factor A (VEGFA) has been found to be upregulated in the articular cartilage, synovium and subchondral bone of OA patients, leading to cartilage degeneration, synovitis and osteophyte formation. However, the functions and mechanisms of LIPUS in regulating chondrocyte‐derived VEGFA expression are still unclear. In this study, we investigated whether LIPUS attenuated OA progression by (a) decreasing the percentage of VEGFA‐positive cells in mouse articular cartilage destabilised through medial meniscus surgery and (b) relieving interleukin‐1β‐induced VEGFA expression in mouse primary chondrocytes. However, this function was negated by a p38 mitogen‐activated protein kinase (p38 MAPK) inhibitor. In addition, we found that LIPUS ameliorated VEGFA‐mediated disorders in cartilage extracellular matrix metabolism and chondrocyte hypertrophy during OA development. In conclusion, our data indicate a novel effect of LIPUS in regulating the expression of osteoarthritic chondrocyte‐derived VEGFA through the suppression of p38 MAPK activity.

Highlights

Osteoarthritis (OA) is the most common joint disease, which affects approximately 40% of the world population aged > 70 years [1]
We investigated whether Low-intensity pulsed ultrasound (LIPUS) attenuated OA progression by (a) decreasing the percentage of vascular endothelium growth factor A (VEGFA)-positive cells in mouse articular cartilage destabilised through medial meniscus surgery and (b) relieving interleukin-1b-induced VEGFA expression in mouse primary chondrocytes
We investigated whether LIPUS attenuated OA progression by decreasing the percentage of VEGFA-positive cells in mouse articular cartilage with destabilisation of the medial meniscus (DMM) surgery and relieving interleukin-1b (IL-1b)-induced VEGFA expression in mouse primary chondrocytes

Summary

Introduction

Osteoarthritis (OA) is the most common joint disease, which affects approximately 40% of the world population aged > 70 years [1]. Low-intensity pulsed ultrasound (LIPUS) is a noninvasive and safe physical therapy [5], which has been widely used in promoting the healing of fresh bone fracture and nonunited fracture [6–8]. A related study has reported that LIPUS increases the vascular endothelium growth factor A (VEGFA) level of periosteal cells in a mouse femur fracture model, facilitating local angiogenesis and promoting fracture healing [15]. Another study reported that either deleting VEGFA in Col Π-Cre lineage cells or intra-articular injecting anti-VEGFA antibody attenuated progression of surgically induced OA in mice [20]. These findings suggest that controlling VEGFA secretion may help prevent OA escalation and OA-associated joint deterioration. The regulation of VEGFA expression in OA articular chondrocytes by LIPUS is still not explicated

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Results

Conclusion