Possible reparative effect of low-intensity pulsed ultrasound (LIPUS) on injured meniscus

Abstract

Menisci are a pair of crescent-shaped fibrocartilages, particularly of which their inner region of meniscus is an avascular tissue. It has characteristics similar to those of articular cartilage, and hence is inferior in healing. We previously reported that low-intensity pulsed ultrasound (LIPUS) treatment stimulates the production of CCN2/CTGF, a protein involved in repairing articular cartilage, and the gene expression of major cartilage matrices such as type II collagen and aggrecan in cultured chondrocytes. Therefore, in this present study, we investigated whether LIPUS has also favorable effect on meniscus cells and tissues. LIPUS applied with a 60 mW/cm 2 intensity for 20 min stimulated the gene expression and protein production of CCN2 via ERK and p38 signaling pathways, as well as gene expression of SOX9, aggrecan, and collagen type II in human inner meniscus cells in culture, and slightly stimulated the gene expression of CCN2 and promoted the migration in human outer meniscus cells in culture. LIPUS also induced the expression of Ccn2, Sox9, Col2a1, and Vegf in rat intact meniscus. Furthermore, histological evaluations showed that LIPUS treatment for 1 to 4 weeks promoted healing of rat injured lateral meniscus, as evidenced by better and earlier angiogenesis and extracellular matrix synthesis. The data presented indicate that LIPUS treatment might prevent meniscus from degenerative change and exert a reparative effect on injured meniscus via up-regulation of repairing factors such as CCN2 and that it might thus be useful for treatment of an injured meniscus as a noninvasive therapy. Keywords CCN2/CTGF. Low-intensity pulsed ultrasound (LIPUS). Meniscal healing. Meniscus regeneration. Cell migration. ERK. p38 Abbreviations CCN Cysteine-rich 61, Connective tissue growth factor, Nephroblastoma-overexpressed CCN2 CCN family member 2, Connective tissue growth factor CCN3 CCN family member 3, Nephroblastomaoverexpressed DMEM Dulbecco's modified Eagle'

Suppression of adipocyte differentiation by low‐intensity pulsed ultrasound via inhibition of insulin signaling and promotion of CCN family protein 2

“…Our previous report revealed that CCN2 was increased in human chondrocytic cells by Dex 32 and in human chondrocytic and meniscus cells by LIPUS treatment. 10,11 Taken together, these findings indicate that Dex or LIPUS treatment in adipogenic cells increased CCN2 production at the mRNA and protein levels, similar to other cells, such as chondrocytes and meniscus cells. Although Dex was capable of inducing PPARγ (Figure 2), it did not induce adipogenesis per se; and LIPUS inhibited adipogenesis (Figure 1).…”

“…Previously, we reported that LIPUS treatment promotes CCN2 production in chondrocytes 10 and meniscus cells. 11 In addition, as we have reported that CCN2 promotes osteoblast differentiation, 23 we tested whether osteoblastic marker genes, such as Runx2, Sp7 (osterix) and Alpl (alkaline phosphatase), are upregulated by LIPUS treatment in adipocyte-committed C3H10T1/2 cells. As shown in Figure 1D panels d-f, LI-PUS treatment did not increase the expression of these osteoblastic marker genes.…”

“…6,7 Recently, anti-inflammatory and chondroprotective effects of LIPUS have been reported, 8,9 and we also reported that LIPUS treatment upregulates the gene expression of aggrecan and type II collagen, which are anabolic factors for chondrocyte differentiation in cultured chondrocytes 10 and that LIPUS promotes the repair of the meniscus tissues in an experimental model of injury to the rat meniscus. 11 In particular, we showed that cellular communication network factor 2 (CCN2) 12 was significantly promoted at the mRNA and protein levels in cultured chondrocytes treated with LI-PUS and that a variety of effects induced by LIPUS treatment are abolished by depletion of CCN2. 10 Based on these data, CCN2 may play central roles in the biological events caused by LIPUS treatment.…”

Roles of Interaction between CCN2 and Rab14 in Aggrecan Production by Chondrocytes

“…The stagnation of vesicular trafficking would therefore enhance the basal ER stress and influence the proteoglycan release and accumulation. We have reported that CCN2 stimulates the mRNA expression of aggrecan in chondrocytic cells [1][2][3] and siRNA against the CCN2 down-regulated mRNA expression of aggrecan in chondrocytic cells [30,31]. However, Rab14 is a protein involved in intracellular membrane trafficking and not a signal inducer, so it is not surprising that Rab14 siRNA had no effect on ACAN mRNA expression.…”

Study of Medical Ultrasound for Rhizarthrosis (SUR): study protocol for a randomized controlled single-center pilot-trial

“…However, recently TUS was reported to improve function, tissue regeneration, and relieve pain via thermal and non-thermal mechanisms in osteoarthritis of the knee [33][34][35][36]. Experimental data suggest that TUS treatment might prevent degenerative changes of the meniscus and exert a reparative effect via activation of cartilage growth factors [37]. Despite such evidence of efficacy, to the best of our knowledge, TUS has never been studied in OAT.…”