Effect of Asymmetric Tension on Biomechanics and Metabolism of Vertebral Epiphyseal Plate in a Rodent Model of Scoliosis

Li, Qianyi; Zhong, Guibin; Liu, Zu‐de; Lao, Li

doi:10.1111/os.12344

Cited by 11 publications

(22 citation statements)

References 36 publications

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“…Our results suggest that the convex side has a lower bone volume than the concave side which is consistent with Wolff’s law, that is, bone formation will increase in areas of compression and decrease in areas of tension. Although previous studies have reported that the convex side shows a higher bone volume than the concave side in a rodent model of scoliosis [41], we assumed that this discrepancy might be because animal models cannot fully reflect the pathophysiology of AIS. In addition, the qPCR, western blotting and immunochemistry also confirmed the imbalance between concave and convex side.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin regulates bone mass in AIS osteopenia via RANKL/OPG and IL6 pathway

et al. 2019

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Background Osteopenia have been well documented in adolescent idiopathic scoliosis (AIS). Adiponectin has been shown to be inversely proportional to body mass index and to affect bone metabolism. However, the circulating levels of adiponectin and the relationship between adiponectin and low bone mass in AIS remain unclear. Methods A total of 563 AIS and 281 age-matched controls were recruited for this study. Anthropometry and bone mass were measured in all participants. Plasma adiponectin levels were determined by enzyme-linked immunosorbent assay (ELISA) in the AIS and control groups. An improved multiplex ligation detection reaction was performed to study on single nucleotide polymorphism. Facet joints were collected and used to measure the microstructure, the expression of RANKL, OPG, osteoblast-related genes, inflammatory factors, adiponectin and its receptors by qPCR, western blotting and immunohistochemistry. Furthermore, primary cells were extracted from facet joints to observe the reaction after adiponectin stimulation. Results Compared with the controls, lower body mass index and a marked increase in circulating adiponectin were observed in AIS osteopenia (17.09 ± 1.09 kg/m 2 and 21.63 ± 10.30 mg/L). A significant difference in the presence of rs7639352 was detected in the AIS osteopenia, AIS normal bone mass and control groups. The T allele showed a significant higher proportion in AIS osteopenia than AIS normal bone mass and control groups (41.75% vs 31.3% vs 25.7%, p < 0.05). micro-CT demonstrated that the AIS convex side had a significant lower bone volume than concave side. RNA and protein analyses showed that in cancellous bone, higher RANKL/OPG and adipoR1 levels and lower runx2 levels were observed, and in cartilage, higher adipoR1 and IL6 levels were observed in AIS. Furthermore, convex side had higher RANKL/OPG, IL6 and adipoR1 than concave side. Compared with normal primary cells, convex side primary cells showed the most acute action, and concave side primary cells showed the second-most acute action when exposed under same adiponectin concentration gradient. Conclusion Our results indicated that high circulating adiponectin levels may result from gene variations in AIS osteopenia. Adiponectin has a negative effect on bone metabolism, and this negative effect might be mediated by the ADR1-RANKL/OPG and ADR1-IL6 pathways. Electronic supplementary material The online version of this article (10.1186/s12967-019-1805-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Adiponectin regulates bone mass in AIS osteopenia via RANKL/OPG and IL6 pathway

et al. 2019

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“…AIS may be caused by abnormal cartilage development. Some researchers found that the imbalanced expression of sox9, collagen II, collagen X, and aggrecan on both sides of the spine may be the cause of scoliosis [46, 47]. Cartilage oligomeric matrix protein (COMP) played a role in maintaining the structural integrity of cartilage.…”

Section: Discussionmentioning

confidence: 99%

A Genetic Variant in GPR126 Causing a Decreased Inclusion of Exon 6 Is Associated with Cartilage Development in Adolescent Idiopathic Scoliosis Population

Shao

Jiang

et al. 2019

BioMed Research International

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Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity disease in adolescents but its etiology and pathogenesis are still unclear. The current study aims to identify the relationship between single nucleotide polymorphisms (SNPs) of G protein-coupled receptor 126 (GPR126) gene and AIS predisposition. GPR126 contains 26 exons and alternative splicing of exon 6 and exon 25 produces 4 protein-coding transcripts. We genotyped SNPs of GPR126 gene around exon 6 and exon 25 in 131 Chinese AIS patients and 132 healthy controls and provided evidence that SNP rs41289839 G>A is strongly associated with AIS susceptibility. Linkage disequilibrium analysis suggests that rs41289839 and other AIS-related SNPs were in strong LD. Next, we demonstrated that rs41289839 G>A inhibits the inclusion of exon 6 during alternative splicing, resulting in a decreased expression level of exon 6-included transcript (GPR126-exon6in) relative to the exon 6 excluded transcript (GPR126-exon6ex) by minigene assay. Chondrogenic differentiation experiment showed that GPR126-exon6in has a high expression level relative to GPR126-exon6ex during chondrogenic differentiation of hMSCs. Our findings indicate that newly discovered SNP is related to cartilage development and may provide valuable insights into the etiology and pathogenesis of adolescent idiopathic scoliosis.

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“…PVM is vital for the stability and functional movement of the spinal column; tension imbalance is a key factor in the initiating or maintaining scoliotic curvature by muscle contraction [33]. The stiffness of concave PVM was greater than that on the convex side in IS patients.…”

Section: Biomed Research Internationalmentioning

confidence: 92%

Exploring the Pathological Role of Collagen in Paravertebral Muscle in the Progression of Idiopathic Scoliosis

Peng

Jin

Meng

et al. 2020

BioMed Research International

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Background. Paravertebral muscle (PVM) is considered as a contributing factor of idiopathic scoliosis (IS); collagen is crucial for maintaining the mechanical properties of PVM, but only a few researches have described this field. In this study, we observed the muscle stiffness of PVM and the curvature of the spine by adjusting the content of collagen in PVM of rats and explored the role of collagen in the progression of IS. Methods. 32 female Sprague Dawley rats were randomly divided into four groups: neutralizing antibody (NA) group (group 1), normal control group (group 2), IS group (group 3), and IS with NA group (group 4). TGF-β1 NA was injected into PVM in group 1 and group 4, while Normal saline in group 2 and group 3. The Cobb angle and muscle stiffness were measured before and after injection; the rats were sacrificed at one week after injection, and performed histological, Western Blot, and qRT-PCR examinations. Results. X-rays showed that scoliosis occurred in group 1 and relieved in group 4. The stiffness of PVM was decreased significantly on the convex side in group 1, while on the concave side in group 4. The expression of TGF-β1 and COL1 on the concave side in IS rats (group 3) was significantly increased than that in normal rats (group 2), the concentration of COL1 and COL3 in group 3 was significantly higher than that in group 2, and the addition of TGF-β1 NA significantly downregulated COL1 and COL3 in group 1 and group 4. The concentration of COL1 in convex PVM was negatively related to Cobb angle in group 1 and group 2, and in concave PVM was positively related to Cobb angle in group 3 and group 4. However, no significant correlation was found between COL3 and Cobb angle in group 3 and group 4. Conclusions. Asymmetric biomechanical characteristics of PVM was an important etiological factor of IS, which was directly correlated with collagen, it could be adjusted by local intramuscular injecting of TGF-β1 NA, and finally had an effect on the shape of the spine.

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Effect of Asymmetric Tension on Biomechanics and Metabolism of Vertebral Epiphyseal Plate in a Rodent Model of Scoliosis

Cited by 11 publications

References 36 publications

Adiponectin regulates bone mass in AIS osteopenia via RANKL/OPG and IL6 pathway

Adiponectin regulates bone mass in AIS osteopenia via RANKL/OPG and IL6 pathway

A Genetic Variant in GPR126 Causing a Decreased Inclusion of Exon 6 Is Associated with Cartilage Development in Adolescent Idiopathic Scoliosis Population

Exploring the Pathological Role of Collagen in Paravertebral Muscle in the Progression of Idiopathic Scoliosis

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