Table 2.
The effects of LIPUS on cartilage.
| PMID | Author (Year) | In vitro study & LIPUS dosage | In vivo study & LIPUS dosage | Main outcomes | |
|---|---|---|---|---|---|
| 11,603,707 | Cook et al. (2001) | N/A | Male New Zealand White rabbits critical-sized osteochondral defect OA model. 30 mW/cm2, 1.5 MHz, 20 min/d for 4, 8, 12, 24, and 52 wk. |
LIPUS improved the morphologic features and histologic characteristics of the repaired cartilage. Better repair at earlier times. A treatment time of 40 min/d increased the histologic quality. | (59) |
| 11,745,554 | Nishikori et al. (2002) | Human primary chondrocytes, 30 mW/cm2, 1.5 MHz, 20 min/d for 3 wk. | N/A | LIPUS promoted the synthesis of CS, especially C6S, although it did not significantly enhance cell number and stiffness. | (60) |
| 12,498,950 | Zhang et al. (2002) | White Leghorn chick embryos sterna explants. 30 mW/cm2, 1.5 MHz, 20 min/d for 1, 3, 5, and 7d. |
N/A | LIPUS increased matrix production. LIPUS increased Col X in certain regions of the sternum. LIPUS stimulated bone formation by increasing hypertrophy of chondrocytes directed to terminal differentiation. | (61) |
| 14,654,159 | Zhang et al. (2003) | White Leghorn chick embryos sterna chondrocytes. 2 and 30 mW/cm2, 1.5 MHz, 20 min/d for 1, 3, 5, and 7d. |
N/A | LIPUS did not affect chondrocyte viability and proliferation. LIPUS acted transiently to decrease the expression of ECM-related genes, followed by up-regulation of Col II and ACAN. LIPUS slowed the progression of chondrocyte hypertrophic differentiation. | (62) |
| 14,689,492 | Duda et al. (2004) | N/A | Hyaline-like cartilage specimens were generated in vitro and subcutaneously implanted in the backs of female homozygotic athymic nude mice, 30 mW/cm2, 1.5 MHz, 20 min/d for 1, 3, 6, and 12 wk. |
LIPUS increased neocartilage formation. The mechanical stability of the neocartilage specimens increased with treatment time and reached values of native cartilage. | (63) |
| 15,896,276 | Jia et al. (2005) | N/A | Male New Zealand White rabbits bilateral full-thickness osteochondral defect OA model, 30 mW/cm2, 1.5 MHz for 8 wk. |
LIPUS increased the scores of the gross appearance grades, histological grades, and the optical density of toluidine blue in the tissues. | (64) |
| 18,359,144 | Tien et al. (2008) | Young children’s primary chondrocytes. 18, 48, 72, and 98 mW/cm2, 1.0 MHz, 20 min/d for 14d. |
N/A | LIPUS increased ACAN synthesis in a time-dependent manner. LIPUS revealed no significant influence on cell proliferation. Human chondrocytes harvested from older donors become less responsive to LIPUS. | (65) |
| 18,483,198 | Cook et al. (2008) | N/A | Male canine osteochondral plugs OA model. 30 mW/cm2, 1.5 MHz, 20 min/d for 6 and 12 wk. |
LIPUS improved the interface repair tissue, which had a more normal translucent appearance. LIPUS improved the cell morphologic characteristics of the interface repair tissue and increased subchondral bone regeneration. | (36) |
| 18,853,213 | Korstjens et al. (2008) | Human primary chondrocytes and cartilage explants. 30 mW/cm2, 1.5 MHz, 20 min/d for 6 d. |
N/A | LIPUS stimulated chondrocyte proliferation and matrix production in human articular cartilage chondrocytes in vitro. | (66) |
| 19,810,106 | Naito et al. (2010) | N/A | Male SD rats ACLT+MMx OA model. 30 mW/cm2, 1.5 MHz, 20 min/d for 7, 14, and 28 d. |
LIPUS increased Col II via the activation of chondrocytes and induction of Col II mRNA expression, thereby exhibiting chondroprotective action. | (67) |
| 20,175,971 | Gurkan et al. (2010) | N/A | Male Hartley guinea pigs joint immobilization OA model. 30 mW/cm2, 1.5 MHz, 20 min/d for 2, 3, 4, 6, 10, 12, 15, and 18 months. |
LIPUS did not fully prevent cartilage degeneration but diminished the severity of the disease. LIPUS decreased the degree of TGF-β1 production. | (68) |
| 20,938,751 | Vaughan et al. (2005) | Steer primary chondrocytes. 30, 100, 200, 300 mW/cm2, 1.5 MHz, 20 min/d for 5, 10, 15, and 20 d. |
N/A | LIPUS (30 mW/cm2) had no net effect on the synthesis of sGAG by adult bovine articular chondrocytes. LIPUS (100 mW/cm2) induced an initial transient up-regulation of SO4 incorporation and sGAG content in agarose constructs. | (69) |
| 21,567,132 | Li et al. (2011) | N/A | Male/female New Zealand white healthy rabbits ACLT OA model. 40 mW/cm2, 3 MHz, 20 min/d, 6d/wk. for 6 wk. |
The early application of LIPUS could delay the degeneration of articular cartilage. This effect was related to the decreased expression of MMP-13 and suppression of ERK1/2, p38 signaling. | (70) |
| 22,920,551 | Ito et al. (2012) | Wistar rat primary chondrocytes. 7.5, 30, and 120 mW/cm2, 1.5 MHz for 1 or 3 h. |
N/A | LIPUS inhibited the induction of MMP13 mRNA expression induced by IL-1β in an intensity-dependent manner. | (71) |
| 23,646,806 | Li et al. (2013) | N/A | New Zealand white healthy rabbits ACLT OA model. 40 mW/cm2, 3 MHz, 20 min/d, 6d/wk. for 4 wk. |
LIPUS decreased the Mankin scores in articular cartilage and inhibited MMP-13 expressions to a large extent through p38, ERK1/2 and JNK pathways. | (72) |
| 24,507,771 | Yang et al. (2014) | N/A | Female Japanese white rabbits critical-sized osteochondral defect OA model. 30 mW/cm2, 1.5 MHz, 20 min/d for 3 months. |
LIPUS did not cause Col II deposition and chondrocyte proliferation. | (73) |
| 24,612,644 | Jang et al. (2014) | Bovine stifle joints, osteochondral explants and CPC. 36.7 mW/cm2, 1 MHz, for 7 d or 27.5 mW/cm2, 3.5 MHz, for 5 min. |
N/A | LIPUS-induced CPC migration was blocked by suppressing FAK phosphorylation with an SFK inhibitor that blocks FAK phosphorylation. | (74) |
| 24,742,749 | Cheng et al. (2014) | Rabbit primary chondrocytes. 40 mW/cm2, 3 MHz, 20 min/d for 6 d. |
Male New Zealand white rabbits ACLT OA model. 40 mW/cm2, 3 MHz, 20 min/d for 6 d. |
LIPUS decreased the degradation of Col II and ACAN, inhibited MMP-1&MMP-13 and activated the integrin-FAK-PI3K/Akt mechanochemical transduction pathway. | (75) |
| 25,571,661 | Xu et al. (2014) | N/A | Female rabbit Hulth OA model. 50 ± 10%mW/cm2, 800 ± 5% kHz, 20 min/d for 2, 4, and 8 wk. |
LIPUS repaired the damaged cartilage by reducing the expression of MMP-3, 7, 13, inhibiting NO secretion and promoting the synthesis of Col II and proteoglycan in cartilage. | (76) |
| 25,267,432 | Tan et al. (2015) | Human and pig cartilage explants. 30 mW/cm2, 1.5 MHz, 20 min/d for 4 wk. |
N/A | LIPUS reduced the expression of the ACAN and Col II genes. LIPUS prevented degenerative changes in pig knee cartilage explants and reduced degeneration in human cartilage samples. | (77) |
| 25,736,607 | Xia et al. (2015) | Rabbit primary chondrocytes. 20, 30, 40 and 50 mW/cm2, 3 MHz, 20 min/d for 6 d. |
Male New Zealand white rabbits ACLT OA model. 20, 30, 40 and 50 mW/cm2, 3 MHz, 20 min/d for 6 d. |
LIPUS affected the expression of Col II and MMP13 through the integrin–p38 MAPK signaling pathway. | (31) |
| 25,915,185 | Ting et al. (2015) | Bovine primary chondrocytes. 55 mW/cm2, 1 MHz, 20 min/d for 10 d. |
N/A | LIPUS increased sGAG and collagen protein production along with a higher Young’s Modulus. LIPUS upregulated gene expression for Col I, Col X, MMP-1, MMP-2, MMP-13, and p-p38. | (23) |
| 26,396,170 | Xia et al. (2015) | N/A | Male New Zealand white Rabbits ACLT OA model. 40 mW/cm2, 3 MHz, 20 min/d, 6d/wk. for 6wk. |
LIPUS protects cartilage from damage in early-stage osteoarthritis via the integrin/FAK/MAPK pathway. | (78) |
| 26,706,677 | Ji et al. (2015) | Rabbit primary chondrocytes. 40 mW/cm2, 3 MHz, 20 min/d for 7d. |
Male New Zealand rabbits inner patellar ligament defect OA model. 40 mW/cm2, 3 MHz, 20 min/d for 7 d. |
LIPUS increased the expression of serum TIMP-2 in the OA model group and decreased MMP-13. | (79) |
| 27,774,951 | Du et al. (2016) | Human primary chondrocytes. 30 mW/cm2, 1.5 MHz, 20 min/d for 7d. |
N/A | LIPUS increased the expressions of Col II and ACAN and reduced MMP-13 via PI3K/Akt pathway. | (80) |
| 27,364,595 | Uddin et al. (2016) | Human cartilage explants, C-28/I2 and C3H10T1/2 cell lines. 30 mW/cm2, 1 MHz, 20 min/d for 7d. |
N/A | LIPUS increased the PG content in human cartilage explants and inhibited IL-1β-induced loss of proteoglycans. LIPUS increased rates of chondrocyte migration and proliferation and promoted chondrogenesis in MSCs. LIPUS suppressed IL-1β-induced activation of p-p65 and p-IκBα, leading to reduced expression of MMP13 and ADAMT5 in chondrocytes. | (30) |
| 27,729,291 | Nishida et al. (2017) | HCS-2/8 cell line, rat primary epiphyseal and articular cartilage cells, and CCN2-deficient chondrocytes. 60 mW/cm2, 3 MHz for 30 min, 1 h, and 5 h. |
N/A | LIPUS-stimulated Ca2+ influx activated chondrocyte differentiation represented by CCN2 production was mediated via MAPK pathways, which in turn was supported by the induced CCN2 molecules in articular chondrocytes. | (24) |
| 28,638,681 | Yılmaz et al. (2017) | N/A | Male SD rats MIA-OA model. 40 mW/cm2, 3 MHz, 20 min/d for 15 d. |
LIPUS had systemic proliferative and regenerative effects on cartilage and tissue. | (44) |
| 29,111,161 | Zahoor et al. (2018) | N/A | Male SD rats IAF-PTOA model. 30 mW/cm2, 1.5 MHz, 20 min/d, 5d/wk. for 2wk. |
LIPUS improved the gait and PTOA pathology of the animals. LIPUS applied at the early stage of IAF or during PTOA development had lasting effects on the PTOA pathology in rat knees. | (81) |
| 29,762,847 | Tang et al. (2018) | N/A | Male/female New Zealand rabbits critical-sized osteochondral defect OA model. 30.0 ± 5.0 mW/cm2, 1.5 MHz, 20 min/d for 4 or 8 wk. |
LIPUS and FGF2 combination promoted the synthesis, secretion of collagen in chondrocytes and the differentiation and maturation of chondrocytes during the repair of cartilage defects. | (82) |
| 30,348,521 | Sekino et al. (2018) | ATDC5 cell line. 30 and 60 mW/cm2, 1.5 MHz, 20 min/d for 3, 5, and 7d. |
N/A | LIPUS induced collagen synthesis and the remodeling of ACAN via the activation of ERK1/2. | (33) |
| 30,262,135 | Hsieh et al. (2018) | N/A | Male SD rats ACLT+MMx OA model. 0.1 W/cm2, 1.0 MHz, 20 min/d for 4 wk. |
LIPUS reduced Mankin scores, inflammatory cells and MMP 13 expression and increased Col II expression in rats with PTOA. | (13) |
| 30,322,672 | Li et al. (2019) | N/A | Female SD rats ACLT OA model. 30 mW/cm2, 3 MHz, 20 min/d, 5d/wk. for 6 wk. |
LIPUS improved cartilage degeneration and subchondral sclerosis during OA progression. | (46) |
| 30,659,392 | Pan et al. (2019) | Rabbit primary chondrocytes. 0.126, 0.157, or 0.25 MPa, 1 MHz, 20 min/d for 7 d. |
N/A | LIPUS plus CCO promoted ECM deposition by accelerating the TGF-β/Smad-signaling pathway in chondrocytes. | (83) |
| 31,975,545 | Guan et al. (2020) | Mouse primary chondrocytes. 30 mW/cm2, 1.5 MHz for 20 min. |
Male C57BL/6 J mice DMM OA model. 30 mW/cm2, 1.5 MHz, 20 min/d for 2 wk. |
LIPUS ameliorated VEGFA-mediated disorders in cartilage ECM metabolism and chondrocyte hypertrophy during OA development. | (34) |
| 33,175,286 | Vahedi et al. (2021) | N/A | Male Bergamasca–Massese sheep critical-sized osteochondral defect OA model. 200 mW/cm2, 20 min/d for 2 months. |
LIPUS induced chondrogenesis by enhancing the proteoglycans, expression of cartilage markers and stimulating the chondrocytes to produce ECM proteins. | (84) |
| 32,281,401 | Sang et al. (2021) | C28/I2 and CHON-001 cell line. 50 or 100 mW/cm2, 1.5 MHz for 24, 48, 72, and 96 h. |
Male C57BL/6 mice ACLT OA model. 40 mW/cm2, 3 MHz, 20 min/d for 8 wk. |
LIPUS improved the arthritis score and weight-bearing abilities. LIPUS reduced IL-6, IL-8 and TNF-α levels in the synovial fluid of OA mice. LIPUS promoted chondrocyte proliferation and differentiation by activating FAK signaling. | (27) |
| 35,184,911 | Tavakoli et al. (2022) | N/A | Male Dunkin Hartley guinea pigs MIA OA model. | LIPUS was superior to PRP in improving the mechanical properties of the articular cartilage, while LIPUS and PRP injection effectively improved joint lubrication. | (85) |
| 35,912,499 | Sabanci et al. (2022) | CHON-001 cell line. 0.5 W/cm2, 3 MHz for 2.5, 5, 7.5, and 10 min. |
N/A | LIPUS induced cartilage cell proliferation; however, no positive effect was observed on cartilage cell migration. | (86) |
| 37,870,591 | Kojima et al. (2023) | N/A | Female ICR mice MIA OA model. 30 mW/cm2, 2 MHz, 20 min/d for 1 or 4 wk. | LIPUS attenuated cartilage degeneration in early OA by relieving inflammation and enhancing the inhibitory effect of lubricin on cartilage degeneration. | (35) |
| 38,517,601 | Wu et al. (2024) | Human and mouse primary chondrocytes. 30 mW/cm2, 1.5 MHz for 20 min. |
C57BL/6 J mice ACLT + PM OA model. 30 mW/cm2, 2 MHz, 20 min/d for 4 wk. |
LIPUS exerted a active effect on OA by activating TRPV4, inducing calcium inward flow, and facilitating the entry of NF-κB into the nucleus to regulate synthetic matrix gene transcription. | (37) |
| 38,493,143 | Pan et al. (2024) | Rat primary chondrocytes. 30, 45, and 60 mW/cm2, 1.5 MHz for 10, 20, and 30 min. |
Male SD rats DMM OA model. 30 mW/cm2, 1.5 MHz, 20 min/d, 5d/wk. for 6wk. |
LIPUS decreased the expression of YAP by restoring the impaired autophagy capacity and inhibiting the binding between YAP and RIPK1, thereby delaying the progression of OA. | (41) |
CS, chondroitin sulfate; Col X, collagen type X; Col II, collagen type II; ACAN, aggrecan; ACLT + MMx, anterior cruciate/medial collateral ligament transection and medial meniscus resection; TGF-β1, transforming growth factor-β1; sGAG, sulphated glycosaminoglycan; MMP, matrix metallopeptidase; ERK, extracellular signal regulated kinases; JNK, Jun N-terminal kinase; CPC, chondrogenic progenitor cell; FAK, focal adhesion kinase; SFK, src family kinase; PI3K, phosphatidylinositol 3-kinase; Akt (PKB), protein kinase B; NO, nitrous oxide; MAPK, mitogen-activated protein kinases; TIMP-2, tissue inhibitor of metalloproteinase-2; MSC, mesenchymal stem cell; PG, proteoglycan; IL, interleukin; IκBα, inhibitor kappa B alpha; ADAMT5, a disintegrin and metalloproteinase with thrombospondin motif 5; CCN2, CCN family protein 2; MIA, monosodium Iodoacetate; IAF-PTOA, intra-articular fracture post-traumatic osteoarthritis; FGF2, fibroblast growth factors; CCO, clematis chinensis osbeck; ECM, extracellular matrix; DMM, destabilization of the medial meniscus; VEGFA, vascular endothelium growth factor A; TNF-α, tumor necrosis factor; PRP, platelet-rich plasma. TRPV4, transient receptor potential channel 4; YAP, Yes-associated protein; RIPK1, receptor-interacting protein kinase 1.