Hypotonic Stress Induces RANKL via Transient Receptor Potential Melastatin 3 (TRPM3) and Vaniloid 4 (TRPV4) in Human PDL Cells

Son, Ga Yeon; Yang, Young-Kyu; Park, Wonse; Chang, Inik; Shin, Dong Min

doi:10.1177/0022034514567196

Cited by 22 publications

(22 citation statements)

References 29 publications

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“…The present results provide new data about the occurrence of putative mechanoproteins in sensory corpuscles, and are the first evidence of the presence of those proteins in the nerves of LCA and tendon-reconstructed LCA. Recently several mechanoproteins were detected in human periodontal ligament, associated and non-associated to neural elements, in particular Ruffini-like corpuscles [32][33][34]. All together, the present results demonstrate that normal human ACL has a rich innervation that is strongly severed after tendon-graft reconstructed ACL, even when if remains partially inserted and after long-term survival.…”

Section: Discussionsupporting

confidence: 61%

Innervation of Partially Inserted Human Tendons Used to Reconstruct Anterior Cruciate Ligament

Ja¹

2017

MOJAP

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Aim: The human anterior cruciate ligament (ACL) provides sensory information to the nervous system that controls the activity of periarticular knee muscles. Thus, ensure the innervation of reconstructed anterior cruciate ligament lead to a better proprioception. Here we investigated the innervation of a unique case of anterior cruciate ligament reconstructed using the semitendinosus and gracilis muscle tendons maintaining the tibial insertions, 12 years after reconstruction. The study was aimed to investigate whether these pieces contain mechanoreceptors and have a pattern of innervation similar to that proper of ACL. Materials and Methods:Immunohistochemistry for general nerve markers (neurons specific enolase, neurofilament proteins, and S100 protein) and putative mechanoproteins (acid-sensing ion channel 2 and transient receptor potential vanilloid 4) was used to map and characterize the nerves in normal ACL and the reconstructed ACL.Results: Perivascular nerves, free nerve endings, Pacini-like and Ruffini-like corpuscles were observed, and mechanoproteins were detected in both free nerve endings and corpuscles, in normal ACL. In the ACL tendon-reconstructed ACL there was a severe reduction in the density of nerve profiles, and especially of sensory corpuscles, which were restricted to the segments closest to the tibial insertion. Conclusion:Normal human ACL has a rich innervation that is strongly severed after tendon-graft reconstructed ACL, even when if remains partially inserted and after long-term survival.

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Section: Discussionsupporting

confidence: 61%

Innervation of Partially Inserted Human Tendons Used to Reconstruct Anterior Cruciate Ligament

Ja¹

2017

MOJAP

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“…Upon knockdown with specific siRNA for TRPM3, the mRNA level of TRPM3 was suppressed (Figure a), whereas the mRNA expression level (Figure b) and the protein expression level (Figure c,d) of Runx2 was increased. Then, cells were exposed to PS and 2‐APB, which are agonist and inhibitor of TRPM3, respectively (Son, Yang, Park, Chang, & Shin, ). As shown in Figure e–g, mRNA and protein levels of Run2 were significantly decreased after the treatment of cells with 100 μM PS, while 75 μM 2‐APB enhanced the expression levels.…”

Section: Resultsmentioning

confidence: 99%

Puerarin inhibits TRPM3/miR‐204 to promote MC3T3‐E1 cells proliferation, differentiation and mineralization

Zeng

Qian

Zhao

et al. 2018

Phytotherapy Research

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Puerarin is an isoflavonoid phytoestrogen extracted from the root of Radix Pueraria, has attracted increasing attention because of its beneficial effects on anti-osteoporosis, but the molecular mechanisms underlying its actions on osteoblasts are not fully understood. The current study aimed to investigate the effect of puerarin on MC3T3-E1 osteoblastic cells proliferation, differentiation and mineralization, in vitro and its underlying mechanisms. The results indicated that puerarin significantly promoted the osteoblasts proliferation, enhanced alkaline phosphatase activity and increased the formation of mineralized nodules. Following treatment with puerarin, the expression levels of transient receptor potential Melastatin 3 (TRPM3) and microRNA-204 (miR-204) were decreased, whereas that of Runt-related transcription Factor 2 (Runx2) increased. TRPM3-small interfering RNA and 2-aminoethoxydiphenyl borate (2-APB, inhibitor of TRPM3) promoted the expression of Runx2 and thus improved the development of osteoblasts, but pregnenolone sulfate, which is the agonist of TRPM3, inhibited the effects. In addition, puerarin induced the changes of intracellular Ca concentration ([Ca ] ) and extracellular Ca concentration ([Ca ] ) through TRPM3 might be involved in the biological process of MC3T3-E1 cells. These results suggested that puerarin may promote MC3T3-E1 cell proliferation, differentiation and mineralization, which may be related to the downregulation of TRPM3/miR-204 and following regulating [Ca ] and [Ca ] , and activation of Runx2.

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“…The roles played by the cytoskeleton in the process of stress-strain-cell signal transduction have been established (35)(36)(37). MScs, particularly TrPV4 and Piezo1, have also been considered key factors in mechanotransduction (8,38). It has been suggested that mechanical loading can induce calcium influx and calcium-dependent cytoskeletal reorganization (39).…”

Section: Discussionmentioning

confidence: 99%

The roles of mechanosensitive ion channels and associated downstream MAPK signaling pathways in PDLC mechanotransduction

et al. 2020

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The present study aimed to investigate whether the cytoskeleton, the Piezo1 ion channel and the transient receptor potential cation channel subfamily V member 4 (TrPV4) ion channel are equally functional in the mechanotransduction of periodontal ligament cells (Pdlcs) and to reveal the interplay of these mechanically sensitive ion channels (MScs). Human Pdlcs (hPdlcs) were pretreated with cytochalasin d (the inhibitor of actin polymerization), GsMTx4 (the antagonist of Piezo1) and GSK205 (the antagonist of TrPV4), and then subjected to periodic mechanical loading. The expression levels of macrophage colony stimulating factor (M-cSF), receptor activator of nF-κB ligand (ranKl) and cyclooxygenase-2 (coX2) in hPdlcs were detected via western blotting. osteoblast mineralization induction capacity of the hPdlcs was also studied and the mitogen-activated protein kinase (MAPK) expression profile was determined via protein microarray. The expression of Piezo1 and TRPV4 in the PDLCs was significantly increased at 8 h after loading. These differences in expression were accompanied by increased expression of M-cSF, ranKl and coX2. compared with the control group, key Pdlc biomarkers were suppressed after mechanical loading following treatment with the inhibitors of Piezo1 (GsMTx4) and TrPV4 (GSK205). The phosphorylated-MAPK protein array showed differential biomarker profiles among all groups. The present study suggested that both MScs and the cytoskeleton participated as mechanical sensors, and did so independently in hPdlc mechanotransduction. Furthermore, the Piezo1 ion channel may transmit mechanical signals via the erK signaling pathway; however, the TrPV4 channel may function via alternative signaling pathways.

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Hypotonic Stress Induces RANKL via Transient Receptor Potential Melastatin 3 (TRPM3) and Vaniloid 4 (TRPV4) in Human PDL Cells

Cited by 22 publications

References 29 publications

Innervation of Partially Inserted Human Tendons Used to Reconstruct Anterior Cruciate Ligament

Innervation of Partially Inserted Human Tendons Used to Reconstruct Anterior Cruciate Ligament

Puerarin inhibits TRPM3/miR‐204 to promote MC3T3‐E1 cells proliferation, differentiation and mineralization

The roles of mechanosensitive ion channels and associated downstream MAPK signaling pathways in PDLC mechanotransduction

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