The effects of pulsed low-intensity ultrasound on chondrocyte viability, proliferation, gene expression and matrix production

Zhang, Mengjie; Huckle, James W.; Francomano, Clair A.; Spencer, Richard G.

doi:10.1016/j.ultrasmedbio.2003.08.011

Cited by 137 publications

(131 citation statements)

References 24 publications

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“…Our results are fairly consistent with previous studies in vitro and in animal models (10,12,13,15). However, Zhang et al showed that the expression of aggrecan and collagen type II was induced by LIUS only at a low intensity of 2 mW/cm 2 in chondrocytes from chick embryos (10).…”

Section: Discussionsupporting

confidence: 93%

“…Immunohistochemical analysis showed that the expression of type II collagen was also increased about 4.5 folds (Figure 3) by LIUS in the chondrocyte pericellular area of the deep layer. The expression of type X collagen was shown in the deep zone of the cartilage explants facing the bone in the control but was decreased about 4.0 folds by the LIUS treatment, suggesting that the LIUS treatment reduces the hypertrophic changes of chondrocytes (10). There was no significant difference in the morphology and the number of chondrocytes between the control and LIUS-stimulated groups.…”

Section: Resultsmentioning

confidence: 80%

“…LIUS was also shown to stimulate the expression of proteoglycan and type II collagen, in a rat fracture model (13) and in a monolayer culture (10,12). Proteoglycan and type II collagen synthesized by chondrocytes are two major components of the extracellular matrix of articular cartilage, and the degradation or decreased synthesis of either protein could lead to significant loss of the cartilage function in patients with arthritic diseases (16,28).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, LIUS has been shown to enhance the healing of fractured bones by inducing chondrocyte proliferation (7,9). When applied to a monolayer culture of human chondrocytes, LIUS also increased cellular proliferation and matrix synthesis (10). In animal studies, LIUS stimulation in both bone fractures and cartilage resulted in increased expression of proteoglycan or type II collagen rather than that of bone formation factors such as transforming growth factor-b (TGF-b), osteocalcin, alkaline phosphatase, and a1(I)-procollagen, hence protecting the collagen matrix and preventing the destruction or degradation of cartilage (11)(12)(13).…”

mentioning

confidence: 99%

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Effects of low‐intensity ultrasound (LIUS) stimulation on human cartilage explants

Min

Woo²,

Cho

et al. 2006

Scandinavian Journal of Rheumatology

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Objective: To evaluate the effects of low-intensity ultrasound (LIUS) stimulation on the anabolic state of human cartilage from patients with osteoarthritis (OA). Methods: Explant cultures of human OA cartilage were stimulated for 10 min every day for 7 consecutive days using continuous-wave sonication at a frequency of 1 MHz with spatial and temporal average intensities of 0 (control), 40, 200, 500, or 700 mW/cm 2 . The effects of LIUS on cell proliferation were evaluated by 3 H-thymidine incorporation. Proteoglycan synthesis was evaluated by the incorporation of 35 S-sulfate and by Safaranin O staining. Collagen synthesis was evaluated by 3 H-proline incorporation and immunohistochemistry. Results: At an intensity of 200 mW/cm 2 , LIUS treatment induced the expression of collagen type II and proteoglycan measured by the incorporation of radioactivity and specific staining of the cartilage explants. However, the expression decreased again at the higher intensities of 500 or 700 mW/cm 2 . Ultrasound had no stimulatory effect on cell proliferation at any intensity. Conclusion: LIUS has anabolic effects on human cartilage in explant cultures, indicating a potentially important method for the repair of osteoarthritic cartilage.Osteoarthritis (OA) is the most common joint disease and is characterized by progressive joint destruction, ultimately leading to the need to replace major joints. Although the precise pathological mechanism has not yet been defined, changes in the function of the chondrocytes are thought to be the main cause of the pathology of OA, particularly the imbalance between the anabolism and the catabolism of the extracellular matrix produced from chondrocytes. Methods to increase synthesis of the cartilage matrix and inhibit its degradation may therefore provide effective treatments for OA.Ultrasound (US) has been used extensively in diagnostic applications (1, 2) and there has recently been increasing interest in its therapeutic use for various musculoskeletal disorders. Several studies have shown that low-intensity US (LIUS) is effective in regenerating injured tissues, including muscles (3, 4) and bones (5-9). In particular, LIUS has been shown to enhance the healing of fractured bones by inducing chondrocyte proliferation (7,9). When applied to a monolayer culture of human chondrocytes, LIUS also increased cellular proliferation and matrix synthesis (10). In animal studies, LIUS stimulation in both bone fractures and cartilage resulted in increased expression of proteoglycan or type II collagen rather than that of bone formation factors such as transforming growth factor-b (TGF-b), osteocalcin, alkaline phosphatase, and a1(I)-procollagen, hence protecting the collagen matrix and preventing the destruction or degradation of cartilage (11-13). However, the effects of LIUS treatment on chondrocyte proliferation and the expression of matrix proteins such as proteoglycan and collagen type II have not been clearly shown in intact human cartilage.In this study, we evaluated the LIUS effects on the ana...

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of low‐intensity ultrasound (LIUS) stimulation on human cartilage explants

Min

Woo²,

Cho

et al. 2006

Scandinavian Journal of Rheumatology

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“…It has been reported that US increases matrix synthesis and that it does not affect the viability or proliferation of chondrocytes (25,26). The procedure reported here caused no harm to joint tissue apart from the proliferation zone in the synovium.…”

Section: Discussionmentioning

confidence: 61%

Microbubble‐enhanced ultrasound exposure promotes uptake of methotrexate into synovial cells and enhanced antiinflammatory effects in the knees of rabbits with antigen‐induced arthritis

Nakaya

Shimizu

Isobe

et al. 2005

Arthritis & Rheumatism

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Objective. To evaluate whether microbubbleenhanced ultrasound (US) treatment promotes the delivery of methotrexate (MTX) into synovial cells and the enhanced antiinflammatory effects of intraarticular MTX therapy in a rabbit arthritis model.Methods. Arthritis was induced in both knees of 53 rabbits by immunization with ovalbumin. MTX including a microbubble agent was then injected into the left and right knee joints, and the right knees were exposed to US (MTX؉/US؉ group), while the left knees were not (MTX؉/US؊ group). The knee joints were evaluated histologically in 7 rabbits at 5 time points up to day 56. Quantitative gene expression of interleukin-1␤ (IL-1␤) in synovial tissue was measured on days 7 and 28. Eight rabbits were used for the measurement of MTX concentration in synovial tissue 12 hours after treatment. To evaluate the effect of microbubble-enhanced US treatment in the absence of MTX, only the microbubble agent was injected into the left and right knee joints of 10 rabbits with or without US exposure, and these animals were evaluated histologically on days 7 and 28.Results. The MTX concentration in synovial tissue was significantly higher in the MTX؉/US؉ group than in the MTX؉/US؊ group. Synovial inflammation was less prominent in the MTX؉/US؉ group compared with the MTX؉/US؊ group, judging from the results of the histologic evaluation and the gene expression levels of IL-1␤ in synovial tissue. It also appeared that microbubble-enhanced US exposure itself did not affect inflammation.Conclusion. Microbubble-enhanced US exposure promoted the uptake of MTX into synovial cells, which resulted in enhancement of the antiinflammatory effects of the intraarticular MTX injection. These results suggest that application of this technique may have clinical benefit.

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Effect of Pulsed Low-Intensity Ultrasonography on Symptom Relief and Tibiofemoral Articular Cartilage Thickness Among Veterans Affairs Enrollees With Knee Osteoarthritis

et al. 2022

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Key Points Question Does 48 weeks of pulsed low-intensity ultrasonography (PLIUS) provide therapeutic benefit for patients with idiopathic knee osteoarthritis? Findings In this randomized clinical trial of 132 adults with symptomatic and radiographic idiopathic knee osteoarthritis, no statistically significant difference was found between PLIUS and sham therapies for clinical symptoms or tibiofemoral cartilage thickness, the coprimary outcomes. Meaning PLIUS as applied in this trial was not effective in ameliorating symptoms or slowing cartilage loss associated with idiopathic knee osteoarthritis.

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The effects of pulsed low-intensity ultrasound on chondrocyte viability, proliferation, gene expression and matrix production

Cited by 137 publications

References 24 publications

Effects of low‐intensity ultrasound (LIUS) stimulation on human cartilage explants

Effects of low‐intensity ultrasound (LIUS) stimulation on human cartilage explants

Microbubble‐enhanced ultrasound exposure promotes uptake of methotrexate into synovial cells and enhanced antiinflammatory effects in the knees of rabbits with antigen‐induced arthritis

Effect of Pulsed Low-Intensity Ultrasonography on Symptom Relief and Tibiofemoral Articular Cartilage Thickness Among Veterans Affairs Enrollees With Knee Osteoarthritis

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