Soluble biglycan: a potential mediator of cartilage degradation in osteoarthritis

Barreto, Gonçalo; Soininen, Antti; Ylinen, Pekka; Sandelin, Jerker; Konttinen, Yrjö T.; Nordström, Dan; Eklund, Kari K.

doi:10.1186/s13075-015-0902-0

Cited by 55 publications

(53 citation statements)

References 50 publications

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“…As described earlier in this narrative, cartilage extracellular matrix fragments such as biglycan, fibronectin, aggrecan and low molecular weight hyaluronan stimulate cell types in the joint via PRRs, leading to the production of inflammatory mediators and the attraction of inflammatory cells, and as such act as alarmins [34][35][36][37]93]. Moreover, they are taken up by synovial macrophages, resulting in the activation of proinflammatory responses in these cells.…”

Section: Alarmins In Osteoarthritismentioning

confidence: 99%

Inflammation in osteoarthritis: is it time to dampen the alarm(in) in this debilitating disease?

Bosch

2018

Clinical and Experimental Immunology

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Summary Osteoarthritis (OA) is the most common joint disease that strongly reduces the quality of life in patients; However, no disease‐modifying therapy is available. For a long time, OA was considered a non‐inflammatory disease that was the result of ‘wear‐and‐tear’ and abnormal mechanics, and therefore many considered the term ‘osteoarthritis’ a misnomer. However, during the last decades the notion arose that inflammation is not only present in the majority of OA patients but, rather, actively involved in the progression of the disease. Influx of immune cells is observed in the synovium and a plethora of inflammatory mediators is present in tissues and fluids from OA patients. These mediators cause the production of degrading enzymes that break down the cartilage matrix, which is the main hallmark of OA. Alarmins, which belong to the group of danger signals, have been implicated in many inflammatory diseases. They are among the first factors to be released upon cell stress due to, for example, infection, damage and inflammation. They attract and activate cells of the immune system and therefore lie at the base of the inflammatory reaction. In this narrative review, an overview of the history of OA, the evolving concept of inflammation as important factor in the OA pathogenesis, and particularly the central role that alarmins play in the initiation and maintenance of the low‐grade inflammatory response in OA, is provided. Moreover, the targeting of alarmins as a promising approach to dampen the inflammation in OA is highlighted.

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Section: Alarmins In Osteoarthritismentioning

confidence: 99%

Inflammation in osteoarthritis: is it time to dampen the alarm(in) in this debilitating disease?

Bosch

2018

Clinical and Experimental Immunology

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“…Here, it might play a role in promoting alignment or in stabilizing such an organization, thereby creating a matrix capable of withstanding load-bearing forces [35]. The slightly decreased COMP expression and the increased pericellular and territorial decorin synthesis demonstrate degeneration-related catabolic changes as described earlier for articular chondrocytes [36,37]. COMP is a target of matrix metalloproteinases, including MMP-13 [38], which have been shown to be upregulated in chondrogenically differentiating mesenchymal stem cells as well as in cardiofibroblasts by targeting the β2-AR [18,39].…”

Section: Discussionmentioning

confidence: 79%

Adrenoceptor Expression during Intervertebral Disc Degeneration

Kupka

Kohler

Bagdadi

et al. 2020

IJMS

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Healthy and degenerating intervertebral discs (IVDs) are innervated by sympathetic nerves, however, adrenoceptor (AR) expression and functionality have never been investigated systematically. Therefore, AR gene expression was analyzed in both tissue and isolated cells from degenerated human IVDs. Furthermore, human IVD samples and spine sections of wildtype mice (WT) and of a mouse line that develops spontaneous IVD degeneration (IVDD, in SM/J mice) were stained for ARs and extracellular matrix (ECM) components. In IVD homogenates and cells α1a-, α1b-, α2a-, α2b-, α2c-, β1-, and β2-AR genes were expressed. In human sections, β2-AR was detectable, and its localization parallels with ECM alterations. Similarly, in IVDs of WT mice, only β2-AR was expressed, and in IVDs of SM/J mice, β2AR expression was stronger accompanied by increased collagen II, collagen XII, decorin as well as decreased cartilage oligomeric matrix protein expression. In addition, norepinephrine stimulation of isolated human IVD cells induced intracellular signaling via ERK1/2 and PKA. For the first time, the existence and functionality of ARs were demonstrated in IVD tissue samples, suggesting that the sympathicus might play a role in IVDD. Further studies will address relevant cellular mechanisms and thereby help to develop novel therapeutic options for IVDD.

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“…The observed presence of intracellular staining might indicate a compensatory effort of the chondrocytes to restore the overall proteoglycan content occurring as a result of the ongoing tissue damage 44 . Moreover, Barreto et al 45 showed that biglycan effectively induces the upregulation of proteinase in early OA stage (stage I), but that this effect is lower in advanced OA stages (stage VI), a condition in which most of the PCM components have already suffered from degradation. As in our ELISA, total biglycan protein content has been shown in radioimmunoassays to be reduced in osteoarthritic cartilage 21 …”

Section: Discussionmentioning

confidence: 99%

Biochemical changes of the pericellular matrix and spatial chondrocyte organization—Two highly interconnected hallmarks of osteoarthritis

Danalache

Erler

Wolfgart

et al. 2020

Journal Orthopaedic Research

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During osteoarthritis, chondrocytes change their spatial arrangement from single to double strings, then to small and big clusters. This change in pattern has recently been established as an image‐based biomarker for osteoarthritis. The pericellular matrix (PCM) appears to degrade together alongside cellular reorganization. The aim of this study was to characterize this PCM‐degradation based on different cellular patterns. We additionally wanted to identify the earliest time point of PCM‐breakdown in this physiopathological model. To this end, cartilage samples were selected according to their predominant cellular pattern. Qualitative analysis of PCM degradation was performed immunohistochemically by analysing five main PCM components: collagen type VI, perlecan, collagen type III, biglycan, and fibrillin‐1 (n = 6 patients). Their protein content was quantified by enzyme‐linked immunosorbent assay (127 patients). Accompanying spatial cellular rearrangement, the PCM is progressively destroyed, with a pericellular signal loss in fluorescence microscopy for collagen type VI, perlecan, and biglycan. This loss in protein signal is accompanied by a reduction in total protein content from single strings to big clusters (P < .001 for collagen type VI, P = .003 for perlecan, and P < .001 for biglycan). As a result of an increase in the number of cells from single strings to big clusters, the amount of protein available per cell also decreases for collagen type III and fibrillin‐1, where total protein levels remain constant. Biochemical changes of the PCM and cellular rearrangement are thus highly interconnected hallmarks of osteoarthritis. Interestingly, the earliest point in time for a relevant PCM impairment appears to be at the transition to small clusters.

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Soluble biglycan: a potential mediator of cartilage degradation in osteoarthritis

Cited by 55 publications

References 50 publications

Inflammation in osteoarthritis: is it time to dampen the alarm(in) in this debilitating disease?

Inflammation in osteoarthritis: is it time to dampen the alarm(in) in this debilitating disease?

Adrenoceptor Expression during Intervertebral Disc Degeneration

Biochemical changes of the pericellular matrix and spatial chondrocyte organization—Two highly interconnected hallmarks of osteoarthritis

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