Abstract:
:End plate chondrocyte degeneration is a major cause of intervertebral disc degeneration. Mechanical biophysical forces, including intermittent cyclic mechanical tension (ICMT), exacerbate end plate chondrocyte degeneration. However, the underlying molecular mechanism of mechanical stretch-induced end plate chondrocyte degeneration is still unclear. This study sought to determine whether microRNAs (miRNAs) respond to mechanical stretch and play a role in regulating mechanically-induced end plate chondrocyte degeneration. We identified miR-365 as a mechanoresponsive miRNA in primary human end plate chondrocytes after ICMT application by miRNA microarray analysis. The expression of miR-365 was down-regulated in the disc samples obtained from patients with disc degeneration. We also found that the miR-365 stimulates chondrocyte proliferation but does not promote end plate chondrocyte death. Using bioinformatic analyses and subsequent confirmation by real-time RT-PCR, we identified multiple candidate target genes of miR-365 that responded to in vitro mechanical stimulation; among them, HDAC4 was fully characterized. Mutation of putative miR-365 binding sites in HDAC4 mRNA abolished miR-365 mediated repression of HDAC4 3'-untranslated region (3'UTR) luciferase reporter activity, suggesting that miR-365 binds to the HDAC4 3'UTR. Overexpression of miR-365 significantly decreased the HDAC4 protein level, suggesting that miR-365 acts as an endogenous attenuator of HDAC4 in human end plate chondrocytes. Further, perturbation of miR-365 expression also had a significant effect on the expression of COL2A and ACAN and on matrix degeneration. Overexpression of HDAC4 abolished miR-365 rescued end plate chondrocyte degeneration during ICMT application. Furthermore, we found that the wnt/β-catenin signal pathway was related to HDAC4 and promoted end plate chondrocyte degeneration. Overall, our results suggest that miR-365 is a mechanosensitive miRNA that regulates human chondrocyte degeneration by directly targeting HDAC4. We propose that therapeutic regulation of miR-365 may be an efficient anabolic strategy for inhibiting end plate chondrocyte degeneration.
journal_name
Bonejournal_title
Boneauthors
Zheng Q,Li XX,Xiao L,Shao S,Jiang H,Zhang XL,Sun LY,Xu HGdoi
10.1016/j.bone.2019.115052subject
Has Abstractpub_date
2019-11-01 00:00:00pages
115052eissn
8756-3282issn
1873-2763pii
S8756-3282(19)30342-4journal_volume
128pub_type
杂志文章相关文献
BONE文献大全abstract::Although ovariectomized cynomolgus monkeys are used extensively for studies examining perimenopausal changes in the skeleton, very little is known about the changes that occur naturally during growth and aging in these animals. To evaluate the changes in bone during growth and aging in female cynomolgus monkeys, 29 mo...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/s8756-3282(98)00149-5
更新日期:1999-01-01 00:00:00
abstract::The accumulation of microdamage in bone may contribute to loss of bone quality in osteoporosis, and the role of microdamage in the etiology of fatigue fractures is unknown. Microdamage created during testing, ex vivo, can increase the fragility of bone by decreasing the load necessary to cause fracture. Microdamage ca...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/s8756-3282(98)00111-2
更新日期:1998-10-01 00:00:00
abstract::Muscle and bone are two intimately connected tissues. A coordinated interplay between these tissues at mechanical levels is required for their development, function and ageing. Evidence is emerging that several genes and molecular pathways exert a pleiotropic effect on both muscle and bone. Bone morphogenetic proteins...
journal_title:Bone
pub_type: 杂志文章,评审
doi:10.1016/j.bone.2015.05.023
更新日期:2015-11-01 00:00:00
abstract::This paper describes a new alternative for individualized mechanical analysis of bone trabecular structure. This new method closes the gap between the classic homogenization approach that is applied to macro-scale models and the modern micro-finite element method that is applied directly to micro-scale high-resolution...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2010.12.022
更新日期:2011-04-01 00:00:00
abstract::Although osteoporosis is usually associated with women, 1 in 12 men in the UK have the disease, and a third of these cases are idiopathic. Estrogen is now known to be associated with bone loss in older men, but we found, previously, that levels of this hormone were normal in younger cases of male idiopathic osteoporos...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/S8756-3282(00)00246-5
更新日期:2000-05-01 00:00:00
abstract::The interrelationship between mediators of hormone action (cAMP and calcium) and induction of ornithine decarboxylase (ODC) activity was investigated in bone and bone cells. Stimuli that enhanced the cAMP level in both osteoblastlike (BL) and osteoclastlike (CL) cells and in intact calvaria only induced ODC activity i...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/8756-3282(85)90405-3
更新日期:1985-01-01 00:00:00
abstract::The objects of this study were to determine the responses of a cancellous bone site with a closed growth plate (the distal tibial metaphysis, DTM) to ovariectomy (OVX) and OVX plus a prostaglandin E2 (PGE2) treatment, and compare the site's response to previous findings reported for another site (the proximal tibial m...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/8756-3282(94)90700-5
更新日期:1994-03-01 00:00:00
abstract::Postmenopausal osteoporosis is characterized by a reduction in the numbers of sinusoidal and arterial capillaries in the bone marrow and reduced bone perfusion suggesting a role of vascular component in the pathogenesis of osteoporosis. Previous studies have shown that bone formation and angiogenesis are positively co...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2011.12.003
更新日期:2012-03-01 00:00:00
abstract::Colony-stimulating factor-1 (CSF-1) induces osteoclast spreading that requires activation of c-Src and phosphatidyl inositol 3-kinase (PI3-K), both of which are recruited to activated c-Fms, the CSF-1 receptor. The present report provides evidence that the hemopoietic guanine nucleotide exchange factor (GEF), Vav, and...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2006.06.012
更新日期:2006-12-01 00:00:00
abstract::Mutations in the GALNT3 gene result in familial tumoral calcinosis, characterized by persistent hyperphosphatemia and ectopic calcific masses in soft tissues. Since calcific masses often recur after surgical removal, a more permanent solution to the problem is required. Nicotinamide is reported to lower serum phosphat...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2014.06.036
更新日期:2014-10-01 00:00:00
abstract::A more accurate understanding of the molecular mechanisms and signaling pathways underpinning human mesenchymal stem cell (MSC) plasticity and differentiation properties is pivotal for accomplishing solid and diligent translation of MSC-based experimental therapeutics and clinical trials to broad clinical practice. In...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2017.10.014
更新日期:2018-01-01 00:00:00
abstract::Skeletal problems and osteoporosis occur in up to 50% affected neurofibromatosis type 1 (NF1) humans. Inactivation of neurofibromin results in deregulation of Ras signal transduction. Little is known of bone biology in humans with NF1. The goal of our work was to determine if loss-of-function of Nf1 gene was associate...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2005.01.022
更新日期:2005-05-01 00:00:00
abstract::The hypocalcemic and hypophosphatemic effect of salmon calcitonin (sCT) given by intranasal (i.n.) spray to 12 patients with histological confirmed primary hyperparathyroidism (1 degree HPT) was studied. The concentration of ionized calcium in whole blood (B-Ca++), serum phosphate (S-P), magnesium (S-Mg), plasma sCT (...
journal_title:Bone
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/8756-3282(91)90016-c
更新日期:1991-01-01 00:00:00
abstract::Paramagnetic manganese can be employed as a calcium surrogate to sensitize the magnetic resonance imaging (MRI) technique to the processing of calcium during the bone formation process. At low doses, after just 48h of exposure, osteoblasts take up sufficient quantities of manganese to cause marked reductions in the wa...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2011.02.014
更新日期:2011-05-01 00:00:00
abstract::Eldecalcitol (ED-71), a 2β-hydroxypropyloxy derivative of 1α,25(OH)(2)D(3), inhibits bone resorption more potently than does alfacalcidol while maintaining osteoblastic function in an estrogen-deficient, high-turnover osteoporosis rat model. Alendronate (ALN) has been reported to increase bone mass by suppressing bone...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2012.02.005
更新日期:2012-05-01 00:00:00
abstract::Metastatic cancer is lethal and patients who suffer bone metastases fare especially poorly. Bone-specific metastatic progression in prostate and breast cancers is a highly observed example of organ-specific metastasis, or organotropism. Though research has delineated the sequential steps of the metastatic cascade, the...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2020.115788
更新日期:2020-12-03 00:00:00
abstract::Hypercalcemia results from an imbalance between the fluxes of calcium (Ca) entering and leaving the extracellular space. The two most important influxes are the net intestinal Ca absorption and the net skeletal Ca resorption, whereas the renal excretion represents the main route of elimination. When produced in excess...
journal_title:Bone
pub_type: 杂志文章,评审
doi:
更新日期:1987-01-01 00:00:00
abstract::Due to the increasing number of osteoporotic fractures of hip, spine, and wrist there is a growing need for methods to track down the subjects with inferior bone structure and to monitor the effects of therapeutic measures. This study aims at a noninvasive diagnostic tool, deriving architectural properties of trabecul...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/s8756-3282(97)00233-0
更新日期:1998-02-01 00:00:00
abstract::We investigated the effect of 2-beta-(3-hydroxypropoxy)-1alpha,25-dihydroxyvitamin D3 (ED-71) on the modeling of bone in distraction osteogenesis. The tibiae of 30 rabbits were lengthened by 10 mm in 10 days. Following osteotomy, ED-71 (0.05 microg/kg) was administered subcutaneously twice a week to the ED-71 group un...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/s8756-3282(98)00179-3
更新日期:1999-03-01 00:00:00
abstract::Osteonecrosis of the jaw (ONJ) is now defined by the presence of exposed bone in the mouth, which fails to heal after appropriate intervention over a period of six or eight weeks. It is commonly precipitated by a tooth extraction in patients treated with zoledronate, pamidronate or a combination of these agents, for t...
journal_title:Bone
pub_type: 杂志文章,评审
doi:10.1016/j.bone.2008.09.012
更新日期:2009-01-01 00:00:00
abstract::Osteocytes have been implicated in the control of bone formation. However, the signal transduction pathways that regulate the biological function of osteocytes are poorly defined. Limited evidence suggests an important role for the Gs/cAMP pathway in osteocyte function. In the present study, we explored the hypothesis...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2013.04.001
更新日期:2013-08-01 00:00:00
abstract::Sulfate conjugation is an important pathway in the metabolism of many drugs, xenobiotic compounds, and hormones. Sulfotransferases (SULTs) catalyze these reactions and have been detected and characterized in various human tissues including the liver and small intestine. Substrates for SULTs that include estrogen and t...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/s8756-3282(01)00463-x
更新日期:2001-06-01 00:00:00
abstract::There is no adequate animal model to mimic the difficult clinical situation of infected non-union of the tibia after intramedullary stabilization. The purpose was to establish an animal model of implant-related infected non-unions of the tibia in rats. Furthermore, it was evaluated if detection of bacteria by fluoresc...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2011.01.018
更新日期:2011-05-01 00:00:00
abstract::The relationships of bone size, bone strength, and bone formation were investigated in two strains of mice, NZB/B1NJ and RF/J. Measurement of the femur midshaft size by peripheral quantitative computed tomography (pQCT) showed that the RF/J mice had a 32% greater cross-sectional area than NZB/B1NJ mice at 10 weeks of ...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/s8756-3282(02)00908-0
更新日期:2002-12-01 00:00:00
abstract::Bone strength in adulthood is known to be affected by health at birth and early childhood. Habitual bone loading is a primary determinant of bone strength in later childhood and adulthood. However, the effects of physical activity in early childhood (e.g. crawling, standing and walking) on bone strength are unknown. F...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2014.08.003
更新日期:2014-11-01 00:00:00
abstract::Osteoclasts are specialized secretory cells of the myeloid lineage important for normal skeletal homeostasis as well as pathologic conditions of bone including osteoporosis, inflammatory arthritis and cancer metastasis. Differentiation of these multinucleated giant cells from precursors is controlled by the cytokine R...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2012.08.113
更新日期:2012-11-01 00:00:00
abstract::Bone turnover occurs at discreet sites in the remodeling skeleton. The focal nature of this process indicates that local cues may facilitate the activation of bone cells by systemic factors. Nucleotides such as adenosine triphosphate (ATP) are locally released, short-lived, yet potent extracellular signaling molecules...
journal_title:Bone
pub_type: 杂志文章,评审
doi:10.1016/s8756-3282(01)00430-6
更新日期:2001-05-01 00:00:00
abstract::We previously reported that calcium intake enhanced the leg bone response to physical activity of preschool children in a 12-month randomized trial of calcium supplementation and physical activity. To determine whether the intervention-induced changes in leg bone mineral content and size were maintained through the su...
journal_title:Bone
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/j.bone.2004.08.012
更新日期:2004-12-01 00:00:00
abstract::Combat-related heterotopic ossification (HO) has emerged as a common and problematic complication of modern wartime extremity injuries, contributing to substantial patient morbidity and loss of function. We have previously reported that HO-forming patients exhibit a more pronounced systemic and local inflammatory resp...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2013.05.016
更新日期:2013-09-01 00:00:00
abstract::The transcription factor nuclear factor E2 p45-related factor 2 (Nrf2) forms heterodimers with small musculoaponeurotic fibrosarcoma (Maf) proteins for the selective recognition of the antioxidant responsive element on target genes, followed by the regulation of gene expression of phase II detoxifying enzymes as well ...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2006.08.016
更新日期:2007-02-01 00:00:00