Overexpression of secretory leukocyte peptidase inhibitor (SLPI) does not modulate experimental osteoarthritis but may be a biomarker for the disease.


OBJECTIVE:Osteoarthritic cartilage destruction can be regulated by the balance between proteases and anti-proteases. Here, we sought to identify novel cellular protease inhibitors associated with osteoarthritis (OA) pathogenesis. METHODS:Candidate molecules were screened from microarray data of chondrocytes treated with OA-associated catabolic factors. The functions of candidate molecules in OA pathogenesis were examined in primary-culture mouse articular chondrocytes and mouse models of OA, such as those stimulated by destabilization of the medial meniscus (DMM) or intra-articular (IA) injection of adenovirus expressing the candidate gene. The value of the selected candidate molecule as a biomarker of OA was examined by measuring its circulating levels in human and mouse blood. RESULTS:Bioinformatic analysis identified secretory leukocyte peptidase inhibitor (SLPI) as a highly upregulated cellular protease inhibitor in chondrocytes treated with pathogenic catabolic factors, including interleukin (IL)-1β, hypoxia-inducible factor (HIF)-2α, and zinc importer ZIP8. The adenovirus-mediated overexpression of SLPI in joint tissues did not cause any OA-like change or modulate DMM- or HIF-2α-induced experimental OA in mice. SLPI also did not markedly modulate the expression of OA-associated catabolic or anabolic factors in chondrocytes. However, SLPI was specifically upregulated in OA cartilage, and the serum SLPI levels were significantly elevated in human OA patients and experimental OA mice, suggesting that SLPI may be a biomarker of OA. CONCLUSION:Although SLPI is upregulated in OA chondrocytes, it does not appear to per se modulate OA development in mice. However, it may be a potential biomarker of OA in humans and animal models.


Kim HE,Shin Y,Jung IJ,Yang JI,Chun CH,Kim HA,Chun JS




Has Abstract


2021-01-21 00:00:00








  • Differences in trabecular bone texture between knees with and without radiographic osteoarthritis detected by directional fractal signature method.

    abstract:OBJECTIVE:To evaluate differences in tibial trabecular bone (TB) texture between subjects with and without radiographic knee osteoarthritis (OA) using a variance orientation transform (VOT) method. DESIGN:Subjects with knee OA (Kellgren & Lawrence grade > or =2) and controls without OA (both n=26, seven women) were ma...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Wolski M,Podsiadlo P,Stachowiak GW,Lohmander LS,Englund M

    更新日期:2010-05-01 00:00:00

  • Patellofemoral morphology and alignment: reference values and dose-response patterns for the relation to MRI features of patellofemoral osteoarthritis.

    abstract:OBJECTIVE:We aimed to (1) determine reference values for trochlear morphology and patellofemoral (PF) alignment in adults without magnetic resonance imaging (MRI)-defined PF full thickness cartilage damage or knee pain; and (2) evaluate dose-response patterns for these measures with prevalent MRI-defined PF structural ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Macri EM,Felson DT,Zhang Y,Guermazi A,Roemer FW,Crossley KM,Khan KM,Stefanik JJ

    更新日期:2017-10-01 00:00:00

  • Long-term effect of removal of knee joint loading on cartilage quality evaluated by delayed gadolinium-enhanced magnetic resonance imaging of cartilage.

    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


    authors: Owman H,Tiderius CJ,Ericsson YB,Dahlberg LE

    更新日期:2014-07-01 00:00:00

  • Premature osteoarthritis in the Disproportionate micromelia (Dmm) mouse.

    abstract:OBJECTIVE:Degeneration of articular cartilage leads to the development of osteoarthritis (OA), but the molecular pathology of the disease is poorly understood. The Disproportionate micromelia (Dmm) mouse has a deletion mutation in the C-propeptide encoding region of Col2a1, which leads to a defective cartilage matrix. ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Bomsta BD,Bridgewater LC,Seegmiller RE

    更新日期:2006-05-01 00:00:00

  • Hypoxia, RONS and energy metabolism in articular cartilage.

    abstract:OBJECTIVE:Increased pro-inflammatory cytokines and reactive oxygen and nitrogen species (RONS) occur in osteoarthritis (OA). Oxygen tension can alter the levels of RONS induced by interleukin-1 (IL-1). RONS such as nitric oxide (NO) can alter energy metabolism. The aim of this study was to determine if oxygen tension a...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Fermor B,Gurumurthy A,Diekman BO

    更新日期:2010-09-01 00:00:00

  • Human genome-wide expression analysis reorients the study of inflammatory mediators and biomechanics in osteoarthritis.

    abstract::A major objective of this article is to examine the research implications of recently available genome-wide expression profiles of cartilage from human osteoarthritis (OA) joints. We propose that, when viewed in the light of extensive earlier work, this novel data provides a unique opportunity to reorient the design o...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,评审


    authors: Sandy JD,Chan DD,Trevino RL,Wimmer MA,Plaas A

    更新日期:2015-11-01 00:00:00

  • Human articular chondrocytes with higher aldehyde dehydrogenase activity have stronger expression of COL2A1 and SOX9.

    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


    authors: Unguryte A,Bernotiene E,Bagdonas E,Garberyte S,Porvaneckas N,Jorgensen C

    更新日期:2016-05-01 00:00:00

  • Should subchondral bone turnover be targeted when treating osteoarthritis?

    abstract:OBJECTIVE:Osteoarthritis (OA) is the most common form of arthritic disease, and it is a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, including bone and cartilage, thereby presenting alternative approaches for treatment. This review summarizes emergi...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,评审


    authors: Karsdal MA,Leeming DJ,Dam EB,Henriksen K,Alexandersen P,Pastoureau P,Altman RD,Christiansen C

    更新日期:2008-06-01 00:00:00

  • Brace treatment for osteoarthritis of the knee: a prospective randomized multi-centre trial.

    abstract:OBJECTIVE:To evaluate the effect of a brace intended to reduce load in patients with medial or lateral compartmental osteoarthritis (OA) and concurrent varus or valgus alignment, respectively. DESIGN:This multi-centre randomized controlled trial (performed 2001-2003) studies the additive effect of a brace intended to ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Brouwer RW,van Raaij TM,Verhaar JA,Coene LN,Bierma-Zeinstra SM

    更新日期:2006-08-01 00:00:00

  • The rs4238326 polymorphism in ALDH1A2 gene potentially associated with non-post traumatic knee osteoarthritis susceptibility: a two-stage population-based study.

    abstract:OBJECTIVE:A recent genome-wide association study reported significant associations of genetic variants within the ALDH1A2 gene with osteoarthritis (OA) of the hand in European populations. However, these findings have not been well generalized to other joints, or to other populations. METHODS:We performed a two-stage ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Chu M,Zhu X,Wang C,Rong J,Wang Y,Wang S,Xing B,Tao Y,Zhuang X,Jiang L

    更新日期:2017-07-01 00:00:00

  • Nitric oxide sustains nuclear factor kappaB activation in cytokine-stimulated chondrocytes.

    abstract:OBJECTIVE:In the current studies we have examined the effects of nitric oxide, and its redox derivatives peroxynitrite and S-nitrosothiol, S-nitrosocysteine, on nuclear factor kappaB (NF-kappaB) activation in cytokine-stimulated bovine chondrocytes. METHODS:The kinetics of NF-kappaB activation (p65 nuclear translocati...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Clancy RM,Gomez PF,Abramson SB

    更新日期:2004-07-01 00:00:00

  • Prevalence of and factors associated with glucosamine use in Canada.

    abstract:OBJECTIVE:Glucosamine is commonly used for the treatment of osteoarthritis, and its use is increasing in the general population. The Canadian Multicentre Osteoporosis Study (CaMos) provided an opportunity to examine the prevalence of glucosamine use across age and gender groups, and to assess the factors associated wit...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,多中心研究


    authors: Hopman WM,Towheed TE,Gao Y,Berger C,Joseph L,Vik SA,Hanley DA,Carran J,Anastassiades T

    更新日期:2006-12-01 00:00:00

  • The groove model of osteoarthritis applied to the ovine fetlock joint.

    abstract:OBJECTIVE:Until now there have been no appropriate models for metacarpophalangeal osteoarthritis (OA), even though OA in this joint is a significant medical and economic problem in horses. A good model would be useful to evaluate progression and treatment of OA, particularly in this joint. Therefore, we translated the ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Mastbergen SC,Pollmeier M,Fischer L,Vianen ME,Lafeber FP

    更新日期:2008-08-01 00:00:00

  • Marked and rapid change of bone shape in acutely ACL injured knees - an exploratory analysis of the Kanon trial.

    abstract:BACKGROUND:To investigate changes in knee 3D bone shape over the first 5 years after acute anterior cruciate ligament (ACL) injury in participants of the randomized controlled KANON-trial. METHODS:Serial MR images over 5 years from 121 young (32 women, mean age 26.1 years) adults with an acute ACL tear in a previously...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,随机对照试验


    authors: Bowes MA,Lohmander LS,Wolstenholme CBH,Vincent GR,Conaghan PG,Frobell RB

    更新日期:2019-04-01 00:00:00

  • Degeneration alters the biomechanical properties and structural composition of lateral human menisci.

    abstract:OBJECTIVE:Because the literature relating to the influence of degeneration on the viscoelasticity and tissue composition of human lateral menisci remains contradictory or completely lacking, the aim of this study was to fill these gaps by comprehensively characterising the biomechanical properties of menisci with regar...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Warnecke D,Balko J,Haas J,Bieger R,Leucht F,Wolf N,Schild NB,Stein SEC,Seitz AM,Ignatius A,Reichel H,Mizaikoff B,Dürselen L

    更新日期:2020-11-01 00:00:00

  • Trabecular bone structure and spatial differences in articular cartilage MR relaxation times in individuals with posterior horn medial meniscal tears.

    abstract:OBJECTIVE:To analyze knee trabecular bone structure and spatial cartilage T(1ρ) and T(2) relaxation times using 3-T magnetic resonance imaging (MRI) in subjects with and without tears of posterior horn of the medial meniscus (PHMM). DESIGN:3-T MRI from 59 subjects (>18 years), were used to evaluate PHMM tears based on...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Kumar D,Schooler J,Zuo J,McCulloch CE,Nardo L,Link TM,Li X,Majumdar S

    更新日期:2013-01-01 00:00:00

  • Ropivacaine- and bupivacaine-induced death of rabbit annulus fibrosus cells in vitro: involvement of the mitochondrial apoptotic pathway.

    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


    authors: Cai XY,Xia Y,Yang SH,Liu XZ,Shao ZW,Liu YL,Yang W,Xiong LM

    更新日期:2015-10-01 00:00:00

  • Bisphosphonates reduce bone mineral loss at ligament entheses after joint injury.

    abstract:OBJECTIVE:To examine the effects of anterior cruciate ligament (ACL) insufficiency, and subsequent bisphosphonate (BP) antiresorptive therapy, on the bone mineral interface at the enthesis of remaining ligamentous restraints. METHODS:We measured bone mineral geometry (and subsequent adaptation) at the medial collatera...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Doschak MR,LaMothe JM,Cooper DM,Hallgrimsson B,Hanley DA,Bray RC,Zernicke RF

    更新日期:2005-09-01 00:00:00

  • Role of subchondral bone properties and changes in development of load-induced osteoarthritis in mice.

    abstract:OBJECTIVE:Animal models recapitulating post-traumatic osteoarthritis (OA) suggest that subchondral bone (SCB) properties and remodeling may play major roles in disease initiation and progression. Thus, we investigated the role of SCB properties and its effects on load-induced OA progression by applying a tibial loading...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Adebayo OO,Ko FC,Wan PT,Goldring SR,Goldring MB,Wright TM,van der Meulen MCH

    更新日期:2017-12-01 00:00:00

  • Expression and function of TbetaRII-B, a variant of the type II TGF-beta receptor, in human chondrocytes.

    abstract:OBJECTIVE:Transforming growth factor-beta (TGF-beta) has profound effects on chondrocyte proliferation and matrix production, and dysregulation of TGF-beta action has been implicated in osteoarthritis. The mechanisms by which the diverse actions of TGF-beta are regulated in chondrocytes are unclear. Although it is well...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Parker WL,Finnson KW,Soe-Lin H,Knaus P,Philip A

    更新日期:2007-04-01 00:00:00

  • Stimulating effect of diacerein on TGF-beta1 and beta2 expression in articular chondrocytes cultured with and without interleukin-1.

    abstract:OBJECTIVE:Diacetylrhein or diacerein has shown efficacy in the treatment of both major forms of osteoarthritis (OA), coxarthrosis as well as gonarthrosis, improving clinical symptoms of the disease (pain reduction and algo-functional index). Both in-vitro and animal models studies suggest that diacerein may have also d...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Felisaz N,Boumediene K,Ghayor C,Herrouin JF,Bogdanowicz P,Galerra P,Pujol JP

    更新日期:1999-05-01 00:00:00

  • Cell and matrix response of temporomandibular cartilage to mechanical loading.

    abstract:OBJECTIVES:The generation of transgenic mice expressing green fluorescent proteins (GFPs) has greatly aided our understanding of the development of connective tissues such as bone and cartilage. Perturbation of a biological system such as the temporomandibular joint (TMJ) within its adaptive remodeling capacity is part...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Utreja A,Dyment NA,Yadav S,Villa MM,Li Y,Jiang X,Nanda R,Rowe DW

    更新日期:2016-02-01 00:00:00

  • Risk factors for osteoarthritis: genetics.

    abstract::Although the multifactorial nature of osteoarthritis (OA) is well recognized, genetic factors have been found to be strong determinants of the disease. Evidence of a genetic influence of OA comes from a number of sources, including epidemiological studies of family history and family clustering, twin studies, and expl...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,评审


    authors: Spector TD,MacGregor AJ

    更新日期:2004-01-01 00:00:00

  • Validity of joint space width measurements in hand osteoarthritis.

    abstract:OBJECTIVE:To investigate the validity of joint space width (JSW) measurements in millimeters (mm) in hand osteoarthritis (OA) patients by comparison to controls, grading of joint space narrowing (JSN), and clinical features. METHODS:Hand radiographs of 235 hand OA patients (mean age 65 years, 83% women) and 471 contro...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Kwok WY,Bijsterbosch J,Malm SH,Biermasz NR,Huetink K,Nelissen RG,Meulenbelt I,Huizinga TW,van 't Klooster R,Stoel BC,Kloppenburg M

    更新日期:2011-11-01 00:00:00

  • Cartilage thickness at the posterior medial femoral condyle is increased in femorotibial knee osteoarthritis: a cross-sectional CT arthrography study (Part 2).

    abstract:OBJECTIVE:To evaluate the thickness of cartilage at the posterior aspect of the medial and lateral condyle in Osteoarthritis (OA) knees compared to non-OA knees using computed tomography arthrography (CTA). DESIGN:535 consecutive knee CTAs (mean patient age = 48.7 ± 16.0; 286 males), were retrospectively analyzed. Kne...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Omoumi P,Michoux N,Roemer FW,Thienpont E,Vande Berg BC

    更新日期:2015-02-01 00:00:00

  • The volume and morphology of chondrocytes within non-degenerate and degenerate human articular cartilage.

    abstract:OBJECTIVE:Cartilage swelling is an early event in osteoarthritis (OA). However, the response of chondrocytes to increased tissue hydration is unknown. This work studied the volume and morphology of living in situ human chondrocytes as a function of cartilage degeneration. METHODS:The tibial plateaus from knee joints o...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Bush PG,Hall AC

    更新日期:2003-04-01 00:00:00

  • Joint distraction in treatment of osteoarthritis: a two-year follow-up of the ankle.

    abstract:OBJECTIVE:Osteoarthritis (OA) is a degenerative joint disease with an incidence exceeding 10% of the adult population. In end stages, OA can result in severe restriction of activity and consequent disability. For these severe cases of OA, no effective remedy is available yet. Joint distraction is a new experimental app...

    journal_title:Osteoarthritis and cartilage

    pub_type: 临床试验,杂志文章,多中心研究


    authors: van Valburg AA,van Roermund PM,Marijnissen AC,van Melkebeek J,Lammens J,Verbout AJ,Lafeber FP,Bijlsma JW

    更新日期:1999-09-01 00:00:00

  • Effects of footwear on the knee adduction moment in medial knee osteoarthritis: classification criteria for flat flexible vs stable supportive shoes.

    abstract:OBJECTIVE:To validate simple criteria that distinguish flat flexible from stable supportive walking shoes by comparing their effects on the knee adduction moment (KAM) in people with medial knee osteoarthritis (OA). DESIGN:This was a cross-sectional biomechanical study. We proposed five criteria to differentiate flat ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,随机对照试验


    authors: Paterson KL,Bennell KL,Wrigley TV,Metcalf BR,Kasza J,Hinman RS

    更新日期:2017-02-01 00:00:00

  • The associations between parity, other reproductive factors and cartilage in women aged 50-80 years.

    abstract:OBJECTIVE:Sex hormones and reproductive factors may be important for osteoarthritis (OA). The aim of this study was to describe the associations of parity, use of hormone replacement therapy (HRT) and oral contraceptives (OCs) with cartilage volume, cartilage defects and radiographic OA in a population-based sample of ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Wei S,Venn A,Ding C,Martel-Pelletier J,Pelletier JP,Abram F,Cicuttini F,Jones G

    更新日期:2011-11-01 00:00:00

  • Localized 3D analysis of cartilage composition and morphology in small animal models of joint degeneration.

    abstract:OBJECTIVE:Current histological scoring methods to evaluate efficacy of potential therapeutics for slowing or preventing joint degeneration are time-consuming and semi-quantitative in nature. Hence, there is a need to develop and standardize quantitative outcome measures to define sensitive metrics for studying potentia...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Thote T,Lin AS,Raji Y,Moran S,Stevens HY,Hart M,Kamath RV,Guldberg RE,Willett NJ

    更新日期:2013-08-01 00:00:00