Effect of Stretching Stress on Gene Transcription Related to Early-phase Differentiation in Rat Periodontal Ligament Cells

Enokiya, Yasunobu; Hashimoto, Sadamitsu; Muramatsu, Takashi; Jung, Han‐Sung; Tazaki, Masakazu; Inoue, Takashi; Abiko, Yoshihiro; Shimono, Masaki

doi:10.2209/tdcpublication.51.129

Cited by 15 publications

(9 citation statements)

References 25 publications

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“…Mechanical loading is also demonstrated to cause similar response. It has been demonstrated that stretching could induce Heat-Shock Proteins (HSPs) upregulation in endothelial cells [13], melanocytes [14], bladder smooth muscle cells [15], vascular smooth muscle cells [16], periodontal ligament cells [17], trabecular meshwork cells [18] and tendon fibroblast [19]. Similar to the IVD, the articular cartilage is also subjected to considerable compressive loading.…”

Section: Introductionmentioning

confidence: 99%

Loading-Induced Heat-Shock Response in Bovine Intervertebral Disc Organ Culture

et al. 2016

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Mechanical loading has been shown to affect cell viability and matrix maintenance in the intervertebral disc (IVD) but there is no investigation on how cells survive mechanical stress and whether the IVD cells perceive mechanical loading as stress and respond by expression of heat shock proteins. This study investigates the stress response in the IVD in response to compressive loading. Bovine caudal disc organ culture was used to study the effect of physiological range static loading and dynamic loading. Cell activity, gene expression and immunofluorescence staining were used to analyze the cell response. Cell activity and cytoskeleton of the cells did not change significantly after loading. In gene expression analysis, significant up-regulation of heat shock protein-70 (HSP70) was observed in nucleus pulposus after two hours of loading. However, the expression of the matrix remodeling genes did not change significantly after loading. Similarly, expressions of stress response and matrix remodeling genes changed with application and removal of the dynamic loading. The results suggest that stress response was induced by physiological range loading without significantly changing cell activity and upregulating matrix remodeling. This study provides direct evidence on loading induced stress response in IVD cells and contributes to our understanding in the mechanoregulation of intervertebral disc cells.

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Section: Introductionmentioning

confidence: 99%

Loading-Induced Heat-Shock Response in Bovine Intervertebral Disc Organ Culture

et al. 2016

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“…In agreement with our results, in one of these studies, BMP-2 was increased by mechanical stimulation, and in another one, by PGE 2 -mediated inflammation [ 12 , 62 ]. Stretch-induced BMP-4, alike BMP-2, was also observed in tendon cells [ 64 ]; however, to our knowledge, no study has demonstrated its osteogenic potential in these cells. Altogether, a local increase in BMPs might modify the mineralizing capacity of entheseal cells to favor ossification in SpA joint.…”

Section: Discussionmentioning

confidence: 99%

Enhanced BMP-2/BMP-4 ratio in patients with peripheral spondyloarthritis and in cytokine- and stretch-stimulated mouse chondrocytes

et al. 2020

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Background Excessive bone formation in the entheses is one of the features of peripheral spondyloarthritis (SpA). Complex pathological mechanisms connecting inflammation, mechanical stress, and ossification are probably involved. We focused on bone morphogenetic protein (BMP)-2, -4, and -7 as possible mediators of this process. Methods BMP-2, -4, and -7 concentration was measured by ELISA in synovial fluids (SFs) of SpA (n = 56) and osteoarthritic (n = 21) patients. Mouse organotypic ankle cultures were challenged by a pro-inflammatory cocktail. Mouse primary chondrocytes, osteoblasts, or tenocytes were treated with TNF-α, interleukin (IL)-17, or IL-22 and/or subjected to cyclic stretch, or with recombinant BMP-2 or -4. Results In SpA SFs, if BMP-7 was barely detectable, BMP-2 concentration was higher and BMP-4 was lower than in osteoarthritic samples, so that BMP-2/BMP-4 ratio augmented 6.5 folds (p < 0.001). In SpA patients, TNF-α, IL-6, and IL-17 levels correlated this ratio (n = 21). Bmp-2/Bmp-4 ratio was similarly enhanced by cytokine treatment in explant and cell cultures, at mRNA level. In particular, simultaneous application of TNF-α and cyclical stretch induced a 30-fold increase of the Bmp-2/Bmp-4 ratio in chondrocytes (p = 0.027). Blockade of prostaglandin E2 and IL-6 production had almost no effect on the stretch-induced regulation of Bmp-2 or -4. Osteoinductive effects of BMP-4, and to a lesser extend BMP-2, were identified on cultured chondrocytes and tenocytes. Conclusions Our results first settle that BMP factors are locally deregulated in the SpA joint. An unexpected decrease in BMP-4 could be associated to an increase in BMP-2, possibly in response to mechanical and/or cytokine stimulations.

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“…Osterix is one of the key factors playing during the osteoblastic cell differentiation just down stream of Runx2, which regulate pre, immature-osteoblasts to matured osteoblast [18][19][20] . At present, some experimental data have been published regarding the gene expression profile of osteoblastic cell differentiation-related factors using IHC [21][22][23][24][25][26][27][28] , but the examination model is limited to in vitro using cultured cells.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Expression of Osterix Appearing in the Mouse Orthodontic Periodontal Tension Sides

Harada

Nakano

Matsuda

et al. 2012

J. Hard Tissue Biology.

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: Early changes of Osterix expression were examined by immunohistochemistry (IHC) and fluorescent immunohistochemistry (FIHC) in mouse periodontal ligament exposed to experimentally induced orthodontic mechanical stress. Eight-week-old ddY mice were used as experimental animals. To provide continuous orthodontic mechanical stress on the periodontal ligament, a rubber dam sheet was placed between the upper molars of the mice. At 20 min, 1 h, 3 h, 9 h and 24 h after the insertion, related parts of the animal tissues were evaluated by IHC and FIHC regarding Osterix and Runx2 expressions. In the 3-h and 9-h experimental groups, orthodontic tension sites reacted positively. The positive reactions became weak in the experimental group at 24-h. The results suggest that Osterix acts as one of the key factors of osteogenic cell differentiation, which expresses the following after the expression of Runx2, down-steam of Runx2.

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Effect of Stretching Stress on Gene Transcription Related to Early-phase Differentiation in Rat Periodontal Ligament Cells

Cited by 15 publications

References 25 publications

Loading-Induced Heat-Shock Response in Bovine Intervertebral Disc Organ Culture

Loading-Induced Heat-Shock Response in Bovine Intervertebral Disc Organ Culture

Enhanced BMP-2/BMP-4 ratio in patients with peripheral spondyloarthritis and in cytokine- and stretch-stimulated mouse chondrocytes

Immunohistochemical Expression of Osterix Appearing in the Mouse Orthodontic Periodontal Tension Sides

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