The influence of pulsed low-intensity ultrasound on matrix production of chondrocytes at different stages of differentiation: an explant study

Zhang, Z.i-Jun; Huckle, James W.; Francomano, Clair A.; Spencer, Richard G.

doi:10.1016/s0301-5629(02)00659-2

Cited by 82 publications

(70 citation statements)

References 22 publications

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“…The data suggest that LIPUS stimulates cartilage matrix production in both degenerative and collateral monolayer cultures and human explants and stimulates chondrocyte proliferation in both degenerative and collateral human explants. This is in agreement with chondrogenic stimulatory effects found by LIPUS treatment in chick embryos, rats and rabbits [2, 16,17,20,21].…”

Section: Discussionsupporting

confidence: 78%

“…This finding is comparable to the results obtained by KopakkalaTani et al [9] who found that chondrocytes obtained from one donor out of five donors remained non-responsive to ultrasound treatment. Several studies have addressed the role of LIPUS as a stimulus for aggrecan synthesis in relation to chondrogenesis [4,16,20,21]. LIPUS stimulated aggrecan mRNA expression and proteoglycan synthesis in rat chondrocytes, and in a rat femur fracture model LIPUS increased mechanical properties of the healing fracture by accelerating synthesis of extra cellular matrix proteins [16,20].…”

Section: Discussionmentioning

confidence: 99%

“…LIPUS not only stimulates bone formation in vitro as well as in vivo [5,10,11,14,15,18], but it also exerts anabolic effects on cartilage formation [2, 13,16,17,[20][21][22]. The stimulatory effect of LIPUS on chondrocytes and cartilage matrix production in fractured bone results in stimulation of the healing process and improves the repair of chondral tissue [2, 12,16,17,20].…”

Section: Introductionmentioning

confidence: 99%

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Low-intensity pulsed ultrasound affects human articular chondrocytes in vitro

Korstjens

Rijt

Albers

et al. 2008

Med Biol Eng Comput

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We investigated whether low-intensity pulsed ultrasound (LIPUS) stimulates chondrocyte proliferation and matrix production in explants of human articular cartilage obtained from donors suffering from unicompartimental osteoarthritis of the knee, as well as in isolated human chondrocytes in vitro. Chondrocytes and explants were exposed to LIPUS (30 mW/cm 2 ; 20 min/day, 6 days). Stimulation of [35 S]-sulphate incorporation into proteoglycans by LIPUS was 1.3-fold higher in degenerative than in collateral monolayers as assessed biochemically and 1.9-fold higher in explants as assessed by autoradiography. LIPUS decreased the number of cell nests containing 1-3 chondrocytes by 1.5 fold in collateral and by 1.6 fold in degenerative explants. LIPUS increased the number of nests containing 4-6 chondrocytes by 4.8 fold in collateral and by 3.9 fold in degenerative explants. This suggests that LIPUS stimulates chondrocyte proliferation and matrix production in chondrocytes of human articular cartilage in vitro. LIPUS might provide a feasible tool for cartilage tissue repair in osteoarthritic patients, since it stimulates chondrocyte proliferation and matrix production.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Low-intensity pulsed ultrasound affects human articular chondrocytes in vitro

Korstjens

Rijt

Albers

et al. 2008

Med Biol Eng Comput

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“…Previously, Zhang et al showed the anabolic effect of LIUS on matrix production in cartilages using the explant cultures of chick embryos (14), but this is the first report on the LIUS effect using intact human cartilages.…”

mentioning

confidence: 99%

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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“…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: 62%

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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The influence of pulsed low-intensity ultrasound on matrix production of chondrocytes at different stages of differentiation: an explant study

Cited by 82 publications

References 22 publications

Low-intensity pulsed ultrasound affects human articular chondrocytes in vitro

Low-intensity pulsed ultrasound affects human articular chondrocytes in vitro

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

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