Chondrocyte primary cilium is mechanosensitive and responds to low-intensity-ultrasound by altering its length and orientation

Low Intensity Pulsed Ultrasound and Articular Cartilage Repair

“…In light of the formidable current and emergent global challenges in managing disabling osteoarthritis in aging populations, along with its limited reversibility, and treatment options, especially those that can foster articular cartilage repair, findings that LIPUS appears to favorably influence anabolic:catabolic cartilage metabolic factor ratios, and can do this consistently in accord with established chondrocyte membrane mechanotransduction and transport mechanisms through variously defined dose parameters, is surely noteworthy, and should not be ignored. To the contrary, it appears that consistent with knowledge that manipulation of the cartilage physical microenvironment by biophysical cues [64] , plus analogous views presented here and others [66][67][68][69][70] , dedicated efforts to extend the findings of LIPUS applications in the context of the laboratory to the clinic is likely to prove highly beneficial to clinicians and others seeking a feasible tool for cartilage tissue repair, as proposed by Korstiens et al [19] , as well as many current or future osteoarthritis sufferers, and should focus on discerning and replicating both its independent effects, as well as its potential utility as an adjunctive or additive therapeutic strategy [21,37,38,71,72] , or both, as far as favorably influencing osteoarthritic articular cartilage reparative, regenerative, and reconstructive processes.…”

“…However, because the chondrocytic mechanotransducing processes initiated or forged by LIPUS may be time sensitive, research to examine an array of timing parameters and/or possible time frames for optimally modulating favorable LIPUS associated outcomes and avoiding unfavorable ones is strongly recommended. As well, examining the relative impact of other LIPUS stimulation parameters as this affects the sensitivity of the chondrocyte membrane and its receptors in both health and disease may help to shed new light on LIPUS and its potential for fostering desirable repair of cartilage defects, especially Figure 1 Schematic representation of the impact of LIPUS on chondrocyte functions that maybe useful for treating osteoarthritis symptoms, and for regenerative cartilage repair efforts as adapted from [5,11,16,19,21,25,26,29,46,47,50,54,63,64,[66][67][68][69][70] osteoarticular cartilage reparative and protective processes. In addition, efforts to carefully examine the impact of LIPUS on multiple chondrocyte cell membrane signaling pathways, and target genes, especially those not previously examined, is strongly encouraged for further examining treatment mechanisms, as is research to examine the utility of matching the frequency of the driving force of LIPUS to that of the chondrocyte system's natural frequency of vibration as outlined by Miller et al [51,52] , and Louw et al [68] .…”

Feasibility of Low Intensity Pulsed Ultrasound to Improve Cartilaginous Thickness in Osteoarthritic Knee

“…According to review article in the role ofLIPUS on osteoarthritis reported that PLIUS alleviated surface irregularities, decreased matrix loss degree with the inhibition of TGF-beta1 production, and attenuated the proceeding of cartilage degeneration in Hartley guinea pigs, which might be an alternative therapy method for human osteoarthritis. LI-PUS down-regulated the Mankin scores and the expression level of MMP-13 in rabbit articular cartilage of animal model of Osteoarthritis [23] .…”

“…Increases in the cilia length were dependent on the duration and pressure-amplitude of the LIUS-signal. US-stimulation also impacted the orientation of the primary cilium in chondrocytes [23] .…”

Galectin 3 Deficiency Alters Chondrocyte Primary Cilium Formation and Exacerbates Cartilage Destruction via Mitochondrial Apoptosis

“…Structural abnormalities of primary cilium morphology altered cilium functions as described in Bbs2 −/− and Bbs4 −/− cilia which displayed a reduced cilium beat frequency compared to normal cilia [33]. Moreover, cilium length regulated anterograde and retrograde ITF transport, protein cargo traffic, protein signaling and mechanical transduction [34,35]. Primary cilium length was regulated by intracellular calcium, AMPc and protein kinase A activation, mechanical compression and osmotic challenge [7,9,34,35].…”