Protective Effects of Low-Intensity Pulsed Ultrasound on Mandibular Condylar Cartilage Exposed to Mechanical Overloading

AbstractThe aim of this study was to examine the role of low-intensity pulsed ultrasound (LIPUS) exposure in the onset and early progression of temporomandibular joint (TMJ) osteoarthritis (TMJ-OA) induced by mechanical overloading. Fifteen-week-old male Wistar rats were divided into two experimental groups and a control group (n = 5 each). In the experimental groups, both TMJs were subjected to mechanical overloading by forced mouth opening using a jaw-opening device for 3 h/day for 5 continuous days. After mechanical overloading, TMJs in one experimental group were exposed to LIPUS for 20 min/day. After the experiments, mandibles were resected from the rats, and the condyles were processed. The bones were analyzed using high-resolution microcomputed tomography (micro-CT). The resected TMJs were also subjected to histological analysis and immunohistochemical staining. Micro-CT images of the mandibular condyle showed severe subchondral trabecular bone loss in the experimental group with overloading. Treatment with LIPUS after overloading resulted in decreased subchondral trabecular bone resorption. In TMJ sections from the experimental group with overloading, cell-free regions and proteoglycan loss characterized the cartilage degradation; LIPUS exposure restricted these changes in the mandibular condyle. Furthermore, the number of tartrate-resistant acid phosphatase-positive osteoclasts in the mineralized layer of the condylar cartilage increased after mechanical overloading and decreased after LIPUS treatment. Our findings suggest that LIPUS exposure after mechanical TMJ overloading downregulates subchondral trabecular bone resorption and proteoglycan loss in the mandibular condylar cartilage. Thus, it may prove to be protective effects of LIPUS exposure on onset and early progression of TMJ-OA induced by mechanical overloading.

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Chondro-protective effects of low intensity pulsed ultrasound

Osteoarthritis and Cartilage ◽

10.1016/j.joca.2016.06.014 ◽

2016 ◽

Vol 24 (11) ◽

pp. 1989-1998 ◽

Cited By ~ 22

Author(s):

S.M.Z. Uddin ◽

B. Richbourgh ◽

Y. Ding ◽

A. Hettinghouse ◽

D.E. Komatsu ◽

...

Keyword(s):

Protective Effects ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity

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The Effect of Low Intensity Pulsed Ultrasound on Proliferation of Rat Condylar Cartilage Cells in Hypoxia Culture

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2019.2023 ◽

2019 ◽

Vol 9 (5) ◽

pp. 630-636

Author(s):

Qiong Li ◽

Wei Geng ◽

Jun Li ◽

Chao Liang ◽

Chaolumen Bao

Keyword(s):

Treatment Effect ◽

Temporomandibular Disorder ◽

Mrna Level ◽

Pulsed Ultrasound ◽

Condylar Cartilage ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Improvement Effect ◽

Cartilage Cells ◽

Subchondral Bone Tissue

Temporomandibular disorder (TMD) is a common and frequently-occurring oral and maxillofacial disease. Restoration of the joint's cartilage and subchondral bone tissue is the key to treat TMD. Low intensity pulsed ultrasound (LIPUS) has been proved to be effective in facilitating chondrocyte's proliferation, which inspired us to probe its treatment effect on TMD. With an isolated and hypoxic cultured mandibular condylar chondrocytes (MCC), we established a model for TMD. HIF-1α and VEGF's mRNA level was increased in hypoxic cultured MCC, which indicates our model simulated the cell's status caused by TMD pathology. When stimulated with LIIPUS at 45 mW/cm2, the MCC's apoptosis rate was inhibited and its proliferation was improved with best efficiency. Further experiment revealed that LIPUS restored MCC's Metalloproteinase's (MMP) up-regulation and collagen II's downregulation in hypoxic cultured MCC, respectively, which might be related to LIPUS's improvement effect on MCC.

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Protective effects of low-intensity pulsed ultrasound on aluminum-induced cerebral damage in Alzheimer's disease rat model

Scientific Reports ◽

10.1038/srep09671 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 53

Author(s):

Wei-Ting Lin ◽

Ran-Chou Chen ◽

Wen-Wei Lu ◽

Shing-Hwa Liu ◽

Feng-Yi Yang

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Rat Model ◽

Protective Effects ◽

Cerebral Damage ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity

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Low-Intensity Pulsed Ultrasound Stimulation of Condylar Growth in Rats

The Angle Orthodontist ◽

10.2319/080708-414.1 ◽

2009 ◽

Vol 79 (5) ◽

pp. 964-970 ◽

Cited By ~ 25

Author(s):

Rodrigo Oyonarte ◽

Mariana Zárate ◽

Francisco Rodriguez

Keyword(s):

Layer Thickness ◽

Mandibular Condyle ◽

Sprague Dawley ◽

Pulsed Ultrasound ◽

Condylar Cartilage ◽

Mandibular Growth ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Bone Level ◽

And Control

Abstract Objective: To test the hypothesis that low-intensity pulsed ultrasound (LIPUS) stimulation does not histologically affect the growth of mandibular condylar cartilage. Materials and Methods: Thirty-five 20-day-old Sprague-Dawley rats were assigned to experimental and control groups. Experimental rats were stimulated with LIPUS in the temporomandibular joint (TMJ) region unilaterally, for 10 or 20 minutes for 20 days. After euthanasia, histological specimens were analyzed qualitatively and histomorphometrically at the anterior and posterior aspects of the mandibular condyle, including the condylar cartilage and the area and perimeter of subchondral bony trabeculae. Results: LIPUS stimulation may alter the histological arrangement of the condylar bone and cartilage, showing qualitative differences on specimens treated for 10 or 20 minutes daily compared with controls. Cartilaginous layer thickness was not affected by LIPUS stimulation to a significant level, but was modified at the relative layer thickness within the cartilage at the anterior aspect of the condyle (P < .05). At the subchondral bone level, 20-minute stimulation significantly increases trabecular perimeter (P = .01). Conclusions: LIPUS application may affect mandibular growth pattern in rats acting at the cartilage and bone level. The effect of LIPUS on the growing condyle is expressed through a variation in trabecular shape and perimeter. A greater response is achieved when stimulated for 20 minutes instead of 10 minutes daily.

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The Attenuating Effect of Low-Intensity Pulsed Ultrasound on Hypoxia-Induced Rat Chondrocyte Damage in TMJ Osteoarthritis Based on TMT Labeling Quantitative Proteomic Analysis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.752734 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sa Du ◽

Chao Liang ◽

Yujie Sun ◽

Bowen Ma ◽

Wenmo Gao ◽

...

Keyword(s):

Treatment Group ◽

Control Group ◽

Pulsed Ultrasound ◽

Condylar Cartilage ◽

Low Intensity Pulsed Ultrasound ◽

Network Analyses ◽

Low Intensity ◽

Hypoxic Conditions ◽

Oxygen Treatment ◽

Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease with a complex and multifactorial etiology. An increased intrajoint pressure or weakened penetration can exacerbate the hypoxic state of the condylar cartilage microenvironment. Our group previously simulated the hypoxic environment of TMJOA in vitro. Low-intensity pulsed ultrasound (LIPUS) stimulation attenuates chondrocyte matrix degradation via a hypoxia-inducible factor (HIF) pathway-associated mechanism, but the mode of action of LIPUS is currently poorly understood. Moreover, most recent studies investigated the pathological mechanisms of osteoarthritis, but no biomarkers have been established for assessing the therapeutic effect of LIPUS on TMJOA with high specificity, which results in a lack of guidance regarding clinical application. Here, tandem mass tag (TMT)-based quantitative proteomic technology was used to comprehensively screen the molecular targets and pathways affected by the action of LIPUS on chondrocytes under hypoxic conditions. A bioinformatic analysis identified 902 and 131 differentially expressed proteins (DEPs) in the <1% oxygen treatment group compared with the control group and in the <1% oxygen + LIPUS stimulation group compared with the <1% oxygen treatment group, respectively. The DEPs were analyzed by gene ontology (GO), KEGG pathway and protein-protein interaction (PPI) network analyses. By acting on extracellular matrix (ECM)-associated proteins, LIPUS increases energy production and activates the FAK signaling pathway to regulate cell biological behaviors. DEPs of interest were selected to verify the reliability of the proteomic results. In addition, this experiment demonstrated that LIPUS could upregulate chondrogenic factors (such as Sox9, Collagen Ⅱ and Aggrecan) and increase the mucin sulfate content. Moreover, LIPUS reduced the hydrolytic degradation of the ECM by decreasing the MMP3/TIMP1 ratio and vascularization by downregulating VEGF. Interestingly, LIPUS improved the migration ability of chondrocytes. In summary, LIPUS can regulate complex biological processes in chondrocytes under hypoxic conditions and alter the expression of many functional proteins, which results in reductions in hypoxia-induced chondrocyte damage. ECM proteins such as thrombospondin4, thrombospondin1, IL1RL1, and tissue inhibitors of metalloproteinase 1 play a central role and can be used as specific biomarkers determining the efficacy of LIPUS and viable clinical therapeutic targets of TMJOA.

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The Optimal Regimen for the Treatment of Temporomandibular Joint Injury Using Low-Intensity Pulsed Ultrasound in Rats with Chronic Sleep Deprivation

BioMed Research International ◽

10.1155/2020/5468173 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Chao Liang ◽

Tao Yang ◽

Gaoyi Wu ◽

Jun Li ◽

Wei Geng

Keyword(s):

Sleep Deprivation ◽

Temporomandibular Joint ◽

Cartilage Damage ◽

Pulsed Ultrasound ◽

Condylar Cartilage ◽

Joint Injury ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Optimal Regimen ◽

Chronic Sleep

Low-intensity pulsed ultrasound (LIPUS) is an emerging physical therapy for the treatment of early temporomandibular joint injury and has a good effect on promoting cartilage and subchondral bone tissue repair. However, the best LIPUS intensity and treatment duration remain unclear. This study is aimed at observing the preventive and therapeutic effects of different modes of LIPUS and at identifying the optimal LIPUS treatment regimen for temporomandibular joint injury. In the present study, rat models of temporomandibular joint injury were established using a chronic sleep deprivation (CSD) method, and the effect of LIPUS as intensities of 30, 45, and 60 mW/cm2 was observed at 7, 14, and 21 days. After CSD, the condylar cartilage of the rats demonstrated variable degrees of surface roughening, collagen fiber disarrangement or even partial exfoliation, decreased proteoglycan synthesis and cartilage thickness, decreased chondrocyte proliferation, decreased type 2 collagen (COL-2) expression, and increased matrix metalloproteinase- (MMP-) 3 expression at all three time points. When the rats with CSD received different intensities of LIPUS treatment, the pathological changes were alleviated to various extents. The groups receiving 45 mW/cm2 LIPUS showed the most significant relief of cartilage damage, and this significant effect was observed on days 14 and 21. These results demonstrated that LIPUS can effectively inhibit CSD-induced condylar cartilage damage in rats, and LIPUS treatment at an intensity of 45 mW/cm2 for at least 2 weeks is the optimal regimen for temporomandibular joint injury.

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