Abstract:
OBJECTIVE:Differentiated articular chondrocytes express a functional bisoform of the leptin receptor (LRb); however, leptin-LRb signaling in these cells is poorly understood. We hypothesized that leptin-LRb signaling in articular chondrocytes functions to modulate canonical Wnt signaling events by altering the expression of Frizzled (FZD) receptors. METHODS:Human chondrocyte cell lines and primary articular chondrocytes were grown in serum containing growth media for 24h, followed by a media change to Dulbecco's modified Eagle's medium (DMEM) containing 1% Nutridoma-SP to obtain a serum-deficient environment for 24h before treatment. Treatments included recombinant human leptin (10-100nM), recombinant human IL-6 (0.3-3nM), or recombinant human erythropoietin (Epo) (10mU/ml). Cells were harvested 30min-48h after treatment and whole cell lysates were analyzed using immunoblots or luciferase assays. RESULTS:Treatment of cells with leptin resulted in activation of Janus kinase 2 (JAK2) and subsequent phosphorylation of specific tyrosine residues on LRb, followed by dose- and time-dependent increases in the expression of Frizzled-1 (FZD1) and Frizzled-7 (FZD7). Leptin-mediated increases in the expression of FZD1 were blocked by pre-treatment with the protein synthesis inhibitor cycloheximide or the JAK2 inhibitor AG490. Experiments using a series of hybrid Epo extracellular domain-leptin intracellular domain receptors (ELR) harboring mutations of specific tyrosine residues in the cytoplasmic tail showed that increases in the expression of FZD1 were dependent on LRb-mediated phosphorylation of STAT3, but not ERK1/2 or STAT5. Leptin pre-treatment of chondrocytes prior to Wnt3a stimulation resulted in an increased magnitude of canonical Wnt signaling. CONCLUSION:These experiments show that leptin-LRb signaling in articular chondrocytes modulates expression of canonical Wnt signaling receptors and suggests that direct cross-talk between these pathways is important in determining chondrocyte homeostasis.
journal_name
Osteoarthritis Cartilagejournal_title
Osteoarthritis and cartilageauthors
Ohba S,Lanigan TM,Roessler BJdoi
10.1016/j.joca.2010.09.006subject
Has Abstractpub_date
2010-12-01 00:00:00pages
1620-9issue
12eissn
1063-4584issn
1522-9653pii
S1063-4584(10)00324-9journal_volume
18pub_type
杂志文章abstract:OBJECTIVE:To characterise longitudinal changes in joint integrity and cartilage volume in vivo in the guinea pig spontaneous osteoarthritis (OA) model by magnetic resonance imaging (MRI). METHODS:Guinea pigs knee were imaged in vivo by high-resolution three-dimensional (3D) MRI between the ages of 3 and 12 months. Ima...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/s1063-4584(03)00162-6
更新日期:2003-12-01 00:00:00
abstract:OBJECTIVE:To evaluate the effect of waiting time on health and quality of life outcomes and costs of medication in total hip replacement (THR) patients in a randomized clinical trial. METHODS:395 THR patients were recruited into the study. When placed on the waiting list, patients were randomized into a short (< or =3...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.joca.2009.03.014
更新日期:2009-09-01 00:00:00
abstract:OBJECTIVE:This study examined within-day osteoarthritis (OA)-related pain patterns and associated patient characteristics. METHODS:Participants with physician diagnoses and self-reported symptoms of hand (N=40), hip (N=32), and knee (N=85) OA recorded pain using a handheld computer on one weekday and one weekend day, ...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2009.03.021
更新日期:2009-10-01 00:00:00
abstract:OBJECTIVE:To determine in human articular chondrocytes the activity of Aldehyde dehydrogenase (ALDH), which are reported as stem/progenitor cell marker in various adult tissues and evaluate gene expression of ALDH1A isoforms. DESIGN:ALDH activity was evaluated by flow cytometry with Aldefluor™ assay in cells, isolated...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2015.11.019
更新日期:2016-05-01 00:00:00
abstract::Human articular cartilage cells were cultured in 1.5% agarose in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal calf serum or in serum-free DMEM with 0.15% bovine serum albumin. 35S-aggrecan synthesis in serum-free DMEM was between 20% and 30% of the value observed in DMEM supplemented with 10% fetal calf se...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/s1063-4584(05)80016-0
更新日期:1995-12-01 00:00:00
abstract:OBJECTIVES:To determine the in vitro effects of oxygen tension on interleukin (IL)-1beta induced nitric oxide (*NO) and prostaglandin E(2) (PGE(2)) production by bovine chondrocytes. DESIGN:Enzymatically isolated bovine chondrocytes were cultured for different periods in suspension in 21 (atmospheric), 5 or 1% (low) o...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2004.09.009
更新日期:2005-01-01 00:00:00
abstract:OBJECTIVE:The purposes of this study were to assess whether local anesthetics (LAs), such as ropivacaine and bupivacaine, could induce apoptosis of rabbit annulus fibrosus (AF) cells in vitro and further to explore the possible underlying mechanism. METHODS:Rabbit AF cells at second passage were treated with saline so...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2015.05.013
更新日期:2015-10-01 00:00:00
abstract:OBJECTIVE:To determine the magnitude of medial femoral cartilage deformation using ultrasonography (US) following walking and running in healthy individuals. DESIGN:Twenty-five healthy participants with no history of osteoarthritis or knee injury volunteered for this study. Medial femoral cartilage thickness was asses...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2016.12.026
更新日期:2017-06-01 00:00:00
abstract:OBJECTIVES:To determine the natural history of cartilage damage and of osteoarthritis (OA) progression using magnetic resonance imaging (MRI); to evaluate whether OA progression varies by stage of disease. METHODS:A population-based cohort with knee pain was assessed clinically, with X-ray (Kellgren-Lawrence [KL] grad...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2011.02.008
更新日期:2011-06-01 00:00:00
abstract:OBJECTIVE:During exercise, cartilage recovers interstitial fluid lost during inactivity, which explains how tissue thickness and joint space are maintained over time. This recovery phenomenon is currently explained by a combination of osmotic swelling during intermittent bath exposure and sub-ambient pressurization dur...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2016.09.018
更新日期:2017-01-01 00:00:00
abstract:OBJECTIVES:The aims of this study were to: 1. Evaluate the performance of arthroscopy for the diagnosis of chondropathy and to compare it to that of direct non-arthroscopic assessments; 2. Determine intra-observer reliability of arthroscopic assessments; 3. Evaluate the effects of the arthroscopic video quality and pro...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2004.12.005
更新日期:2005-05-01 00:00:00
abstract:OBJECTIVES:Knee osteoarthritis (OA) onset and progression has been defined with transitions in Kellgren-Lawrence (KL) grade or Osteoarthritis Research Society International (OARSI) Joint Space Narrowing (JSN) grade. We quantitatively describe one-year transitions in KL grade and JSN, using fixed joint space width (fJSW...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2018.05.014
更新日期:2018-09-01 00:00:00
abstract:OBJECTIVE:To develop a model of early osteoarthritis, by examining whether radiographically normal knees with contralateral joint space narrowing (JSN), but without contralateral trauma history, display greater longitudinal cartilage composition change (transverse relaxation time; T2) than subjects with bilaterally nor...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2019.06.013
更新日期:2019-11-01 00:00:00
abstract:OBJECTIVE:Because articular cartilage has limited ability to repair itself, treatment of (osteo)chondral lesions remains a clinical challenge. We aimed to evaluate how well a tissue-engineered cartilage-like implant, derived from chondrocytes cultured in a novel patented, scaffold-free bioreactor system, would perform ...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1053/joca.2001.0438
更新日期:2001-01-01 00:00:00
abstract:OBJECTIVE:Implantation of autologous chondrocytes (AC) is a promising option for the treatment of cartilage defects, but problems with cell harvesting, dedifferentiation, or the donor age limit the clinical outcome. Mesenchymal stem cells (MSC) gain much interest because of their simple isolation and multipotential dif...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2009.10.015
更新日期:2010-03-01 00:00:00
abstract:OBJECTIVE:To elucidate the role of LRRK2 in intervertebral disc degeneration (IDD) as well as its mitophagy regulation mechanism. METHODS:The expression of LRRK2 in human degenerative nucleus pulposus tissues as well as in oxidative stress-induced rat nucleus pulposus cells (NPCs) was detected by western blot. LRRK2 w...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2021.01.002
更新日期:2021-01-09 00:00:00
abstract:OBJECTIVE:The objective of this study was to evaluate the feasibility of quantifying the Equilibrium Partitioning of an Ionic Contrast agent via Microcomputed Tomography (EPIC-microCT) to nondestructively assess sulfated glycosaminoglycan (sGAG) content and distribution in rat articular cartilage ex vivo, and in doing ...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2009.07.014
更新日期:2010-01-01 00:00:00
abstract:OBJECTIVE:Ankle fracture patients were used as a model to study the long-term effect of the removal of joint loading on knee cartilage quality in human subjects. DESIGN:The knees of 10 patients with ipsilateral ankle fractures were investigated using delayed gadolinium-enhanced magnetic resonance imaging of cartilage ...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2014.04.021
更新日期:2014-07-01 00:00:00
abstract:OBJECTIVE:In this population-based cohort study, we examined the association between the presence of symptomatic osteoarthritis (OA) and risk for cardiovascular (CV) events. METHOD:A cohort aged ≥55 years recruited from 1996 to 98 was followed through provincial health administrative data to 2014. Demographics, joint ...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2017.07.024
更新日期:2017-11-01 00:00:00
abstract:OBJECTIVE:Chondrocytes are highly sensitive to variations in extracellular glucose and oxygen levels in the extracellular matrix. As such, they must possess a number of mechanisms to detect and respond to alterations in the metabolic state of cartilage. In other organs such as the pancreas, heart and brain, such detect...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2006.06.017
更新日期:2007-01-01 00:00:00
abstract:OBJECTIVES:To address the hypothesis that different types of established osteoarthritis (OA) pain behaviours have associations with different aspects of articular pathology, we investigated the relationship between structural knee joint pathology and pain behaviour following injection of a low vs a high dose of monosod...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2016.06.012
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:Arthroscopic partial meniscectomy (APM) is the most frequently performed orthopedic procedure. Functional outcomes of APM are variable, particularly among patients with underlying knee osteoarthritis. While most patients undergoing APM have knee magnetic resonance imaging (MRI) performed preoperatively, the ...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2005.11.014
更新日期:2006-05-01 00:00:00
abstract:OBJECTIVES:To examine the in situ distributions of vitamin D receptors (VDR) and matrix metalloproteinases (MMPs) in osteoarthritic cartilage for comparison with non-arthritic, normal cartilage; and to assess the in vitro effects of 1alpha,25 dihydroxyvitaminD(3)(1alpha,25(OH)(2)D(3)) on MMPs-1, -3 and -9 and prostagla...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1053/joca.2000.0408
更新日期:2001-07-01 00:00:00
abstract:OBJECTIVE:To assess if various biological responses to transforming growth factor-beta (TGF-beta) in chondrocytes are differentially regulated by Smad-6 and Smad-7. DESIGN:Adenoviral overexpression of Smad-6 or -7 mRNA in a chondrocyte cell line was determined via semi-quantitative RT-PCR and protein overexpression wa...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/s1063-4584(03)00165-1
更新日期:2003-11-01 00:00:00
abstract:OBJECTIVE:Statistical shape modelling (SSM) of hip dual-energy X-ray absorptiometry (DXA) scans has identified relationships between hip shape and radiographic hip OA (rHOA). We aimed to further elucidate shape characteristics related to rHOA by focusing on subregions identified from whole-hip shape models. METHOD:SSM...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2020.04.011
更新日期:2020-08-01 00:00:00
abstract:OBJECTIVE:Investigate whether body mass index (BMI), comorbidity, gender and age predict patient-reported functional limitation 2- and 5-years after primary Total Knee Arthroplasty (TKA). METHODS:Overall moderate-severe activity limitation was defined as > or = 2 activities (walking, stairs, rising from chair) with mo...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2009.12.001
更新日期:2010-04-01 00:00:00
abstract:OBJECTIVE:The European Society on Clinical and Economic aspects of Osteoporosis and Osteoarthritis (ESCEO) organised a working group to evaluate the need for updating the current European guideline on clinical investigation of drugs used in the treatment of osteoarthritis (OA). DESIGN:Areas of potential attention were...
journal_title:Osteoarthritis and cartilage
pub_type: 共识发展会议,杂志文章,评审
doi:10.1016/j.joca.2015.07.001
更新日期:2015-12-01 00:00:00
abstract:OBJECTIVE:The objective of this study is to characterize mouse temporomandibular joint (TMJ) following partial discectomy, since there is no documentation of whether or not partial discectomy can induce early-onset osteoarthritis (OA) in mouse TMJ. METHODS:Partial discs of TMJ in mice were removed by microsurgery. His...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2009.01.002
更新日期:2009-07-01 00:00:00
abstract:PURPOSE:Our aim was to introduce a simplified MRI instrument, Rapid OsteoArthritis MRI Eligibility Score (ROAMES), for defining structural eligibility of patients for inclusion in disease-modifying osteoarthritis drug trials using a tri-compartmental anatomic approach that enables stratification of knees into different...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2019.08.005
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVE:To compare measurement properties of the P4 pain scale, Western Ontario and McMaster Universities Arthritis Index pain subscale (WOMAC-pain), and Intermittent and Constant Osteoarthritis Pain (ICOAP) measure in patients with knee osteoarthritis (OA). DESIGN:A secondary analysis from a randomized controlled t...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.joca.2014.03.018
更新日期:2014-06-01 00:00:00