Systemic and local adipose tissue in knee osteoarthritis

Chang, Jun; Liao, Zetao; Lu, Ming; Meng, Tao; Han, Weiyu; Ding, Changhai

doi:10.1016/j.joca.2018.03.004

Cited by 77 publications

(67 citation statements)

References 88 publications

(81 reference statements)

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“…Thigh muscle deficits [1,2] and accumulation of (local) adipose tissue [3][4][5] are important pathophysiological events in the context of the clinical science and management of musculoskeletal diseases such as knee osteoarthritis (OA) [1]. Muscles play an essential role in stabilizing the joints [1,6], while excessive adipose tissue may induce a chronic inflammatory state by producing adipokines and inflammatory cytokines.…”

Section: Introductionmentioning

confidence: 99%

“…Muscles play an essential role in stabilizing the joints [1,6], while excessive adipose tissue may induce a chronic inflammatory state by producing adipokines and inflammatory cytokines. Both are suggested to be involved in cartilage degradation, synovial inflammation, and bone erosion [3,4]. Magnetic resonance imaging (MRI)-based analysis is increasingly used to study the association between thigh muscle and adipose tissue composition with knee OA [7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Clinical evaluation of fully automated thigh muscle and adipose tissue segmentation using a U-Net deep learning architecture in context of osteoarthritic knee pain

Kemnitz

Baumgartner

Eckstein

et al. 2019

Magn Reson Mater Phy

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Objective Segmentation of thigh muscle and adipose tissue is important for the understanding of musculoskeletal diseases such as osteoarthritis. Therefore, the purpose of this work is (a) to evaluate whether a fully automated approach provides accurate segmentation of muscles and adipose tissue cross-sectional areas (CSA) compared with manual segmentation and (b) to evaluate the validity of this method based on a previous clinical study. Materials and methods The segmentation method is based on U-Net architecture trained on 250 manually segmented thighs from the Osteoarthritis Initiative (OAI). The clinical evaluation is performed on a hold-out test set bilateral thighs of 48 subjects with unilateral knee pain. Results The segmentation time of the method is < 1 s and demonstrated high agreement with the manual method (dice similarity coeffcient: 0.96 ± 0.01). In the clinical study, the automated method shows that similar to manual segmentation (− 5.7 ± 7.9%, p < 0.001, effect size: 0.69), painful knees display significantly lower quadriceps CSAs than contralateral painless knees (− 5.6 ± 7.6%, p < 0.001, effect size: 0.73). Discussion Automated segmentation of thigh muscle and adipose tissues has high agreement with manual segmentations and can replicate the effect size seen in a clinical study on osteoarthritic pain.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical evaluation of fully automated thigh muscle and adipose tissue segmentation using a U-Net deep learning architecture in context of osteoarthritic knee pain

Kemnitz

Baumgartner

Eckstein

et al. 2019

Magn Reson Mater Phy

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“…Historically, degeneration of articular cartilage has been a major focus of studies on the etiopathogenesis of OA. However, with the appreciation of OA as a multifactorial global disorder and that degenerative changes in cartilage are affected by degeneration in the synovium, subchondral bone, infra-patellar fat pad, meniscus, ligaments and tendons [43][44][45][46][47][48][49][50][51][52][53] there is now a greater appreciation of contributions from all these joint tissues in the achievement of optimal knee functional properties [54][55][56][57]. inhibiting the migration of melanoma cells and cell-matrix interactions required to promote tumor progression [30,67].…”

Section: Resultsmentioning

confidence: 99%

Catabolism of Fibromodulin in Developmental Rudiment and Pathologic Articular Cartilage Demonstrate Novel Roles for MMP-13 and ADAMTS-4 in C-Terminal Processing of SLRPs

Shu¹,

Flannery²,

Little³

et al. 2018

Preprint

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Cartilage regeneration requires a balance of anabolic and catabolic processes. This study examined the susceptibility of fibromodulin (FMOD) and lumican (LUM) to degradation by MMP-13, ADAMTS-4 and ADAMTS-5, the three major degradative proteinases in articular cartilage in osteoarthritis (OA). Immunolocalisation of FMOD and LUM in foot sections of developmental cartilages demonstrated prominent localisations in metatarsal and phalangeal foetal rudiment cartilages and growth plate. An MMP-13 neoepitope antibody (TsYG11) demonstrated localisation of MMP-13 cleaved FMOD in the hypertrophic chondrocytes of the metatarsal growth plate. FMOD was more prominently localised in the superficial cartilage of normal and fibrillated zones in OA cartilage, TsYG11 positive FMOD was located deeper in the cartilage samples. Ab TsYG11 also identified FMOD fragmentation in Western blots of extracts of normal and fibrillated cartilage and total knee replacement OA cartilage.  The C-terminal anti-FMOD used in this study (PR-184) failed to identify FMOD fragmentation due to C terminal processing, an equivalent Ab to the C-terminus of LUM (pAb PR-353) identified 3 prominent LUM fragments in OA human knee cartilages. In-vitro digestion of human knee cartilage with MMP-13, ADAMTS-4 and ADAMTS-5 generated equivalently sized FMOD fragments of 54, 45 and 32kDa to those in blots of OA cartilage, LUM was not less susceptible to fragmention in in-vitro digestions however Ab PR-353 detected N-terminally processed LUM fragments of 39, 38 and 22 kDa in 65-80 year old OA knee cartilage. FMOD and LUM were differentially processed during in-vitro digestions with MMP-13, ADAMTS-4 and ADAMTS-5 with FMOD susceptible to degradation by MMP-13, ADAMTS-4 and to a lesser extent ADAMTS-5 however LUM was less susceptible to fragmentation. FMOD was processed by MMP-13 in metatarsal and phalangeal foetal rudiment developmental cartilages and growth plate indicating a role in skeletogenesis.

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“…Current clinical applications include scar treatment, breast reconstruction after breast cancer surgery, aesthetic rejuvenation, cleft-lip repair and liposculpture for body deformities [30,[33][34][35][36]. The treatment of bone defects, osteomyelitis or chronic wounds is being debated [13,30,[35][36][37][38][39]. Although having a higher immunomodulatory and regenerative potential, the clinical use of purified ADSCs is, as mentioned above, even more restricted.…”

Section: Introductionmentioning

confidence: 99%

Differences in the Inflammatory Response of White Adipose Tissue and Adipose-Derived Stem Cells

Taha

Volkmer

Haas

et al. 2020

IJMS

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The application of liposuctioned white adipose tissue (L-WAT) and adipose-derived stem cells (ADSCs) as a novel immunomodulatory treatment option is the currently subject of various clinical trials. Because it is crucial to understand the underlying therapeutic mechanisms, the latest studies focused on the immunomodulatory functions of L-WAT or ADSCs. However, studies that examine the specific transcriptional adaptation of these treatment options to an extrinsic inflammatory stimulus in an unbiased manner are scarce. The aim of this study was to compare the gene expression profile of L-WAT and ADSCs, when subjected to tumor necrosis factor alpha (TNFα), and to identify key factors that might be therapeutically relevant when using L-WAT or ADSCs as an immuno-modulator. Fat tissue was harvested by liposuction from five human donors. ADSCs were isolated from the same donors and shortly subjected to expansion culture. L-WAT and ADSCs were treated with human recombinant TNFα, to trigger a strong inflammatory response. Subsequently, an mRNA deep next-generation sequencing was performed to evaluate the different inflammatory responses of L-WAT and ADSCs. We found significant gene expression changes in both experimental groups after TNFα incubation. However, ADSCs showed a more homogenous gene expression profile by predominantly expressing genes involved in immunomodulatory processes such as CCL19, CCL5, TNFSF15 and IL1b when compared to L-WAT, which reacted rather heterogeneously. As RNA sequencing between L-WAT and ADSCS treated with TNFα revealed that L-WAT responded very heterogeneously to TNFα treatment, we therefore conclude that ADSCs are more reliable and predictable when used therapeutically. Our study furthermore yields insight into potential biological processes regarding immune system response, inflammatory response, and cell activation. Our results can help to better understand the different immunomodulatory effects of L-WAT and ADSCs.

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Systemic and local adipose tissue in knee osteoarthritis

Cited by 77 publications

References 88 publications

Clinical evaluation of fully automated thigh muscle and adipose tissue segmentation using a U-Net deep learning architecture in context of osteoarthritic knee pain

Clinical evaluation of fully automated thigh muscle and adipose tissue segmentation using a U-Net deep learning architecture in context of osteoarthritic knee pain

Catabolism of Fibromodulin in Developmental Rudiment and Pathologic Articular Cartilage Demonstrate Novel Roles for MMP-13 and ADAMTS-4 in C-Terminal Processing of SLRPs

Differences in the Inflammatory Response of White Adipose Tissue and Adipose-Derived Stem Cells

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