Decorin regulates cartilage pericellular matrix micromechanobiology

Chery, Daphney R.; Han, Biao; Zhou, Ying; Wang, Chao; Adams, Sheila M.; Chandrasekaran, Prashant; Kwok, Bryan; Heo, Su‐Jin; Enomoto‐Iwamoto, Motomi; Lü, Xin; Kong, Dehan; Iozzo, Renato V.; Birk, David E.; Mauck, Robert L.; Han, Lin

doi:10.1016/j.matbio.2020.11.002

Cited by 42 publications

(39 citation statements)

References 100 publications

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“…In DCN null mice (Dcn −/− ), the modulus of the PCM is significantly reduced from 2 weeks of age onwards concomitant with the absence of a maturation-associated stiffening effect [65]; similar effects were also observed in the TM/ITM consistent with the finding that, at the tissue level, DCN loss results in a reduced cartilage modulus at ≥2 weeks of age. Impairment of the PCM because of a loss of DCN also affected Ca 2+ signalling and thus the chondrocytes response to load [65]. Dcn −/− cartilage has a significantly reduced aggrecan component and mild perturbations in collagen fibril nanostructure resulting in inferior biomechanical properties as evidenced by a decreased modulus and elevated hydraulic permeability [99].…”

Section: The Pericellular Matrix and Its Role In Chondrocyte Mechanotransductionsupporting

confidence: 81%

“…Experimental studies and theoretical models have demonstrated that the PCM facilitates the transduction of both biomechanical and biochemical signals to the residing chondrocytes [58][59][60][61], thereby regulating the process of mechanotransduction in the chondrocyte [30,57,[62][63][64]. To facilitate this, the PCM is softer than the rest of the ECM [39,65] but has a higher modulus than the cell [66] acting as a biomechanical buffer [67] to control the deformation applied to the cell [68]. In addition, the PCM regulates chondrocyte phenotype [69], with cell survival directly dependant on the interactions between the chondrocyte and the PCM [70,71], and acts as a biological reservoir sequestering growth factors and signalling molecules [72][73][74][75].…”

Section: The Pericellular Matrix and Its Role In Chondrocyte Mechanotransductionmentioning

confidence: 99%

“…DCN knockdown results in an increase in aggrecan, BGN and sox9 gene expression early in chondrogenesis and prevents the formation of a normal microfibrillar layer surrounding the cell [88]. In DCN null mice (Dcn −/− ), the modulus of the PCM is significantly reduced from 2 weeks of age onwards concomitant with the absence of a maturation-associated stiffening effect [65]; similar effects were also observed in the TM/ITM consistent with the finding that, at the tissue level, DCN loss results in a reduced cartilage modulus at ≥2 weeks of age. Impairment of the PCM because of a loss of DCN also affected Ca 2+ signalling and thus the chondrocytes response to load [65].…”

Section: The Pericellular Matrix and Its Role In Chondrocyte Mechanotransductionmentioning

confidence: 99%

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Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage

Gilbert

Bonnet

Blain

2021

IJMS

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The composition and organisation of the extracellular matrix (ECM), particularly the pericellular matrix (PCM), in articular cartilage is critical to its biomechanical functionality; the presence of proteoglycans such as aggrecan, entrapped within a type II collagen fibrillar network, confers mechanical resilience underweight-bearing. Furthermore, components of the PCM including type VI collagen, perlecan, small leucine-rich proteoglycans—decorin and biglycan—and fibronectin facilitate the transduction of both biomechanical and biochemical signals to the residing chondrocytes, thereby regulating the process of mechanotransduction in cartilage. In this review, we summarise the literature reporting on the bidirectional reciprocity of the ECM in chondrocyte mechano-signalling and articular cartilage homeostasis. Specifically, we discuss studies that have characterised the response of articular cartilage to mechanical perturbations in the local tissue environment and how the magnitude or type of loading applied elicits cellular behaviours to effect change. In vivo, including transgenic approaches, and in vitro studies have illustrated how physiological loading maintains a homeostatic balance of anabolic and catabolic activities, involving the direct engagement of many PCM molecules in orchestrating this slow but consistent turnover of the cartilage matrix. Furthermore, we document studies characterising how abnormal, non-physiological loading including excessive loading or joint trauma negatively impacts matrix molecule biosynthesis and/or organisation, affecting PCM mechanical properties and reducing the tissue’s ability to withstand load. We present compelling evidence showing that reciprocal engagement of the cells with this altered ECM environment can thus impact tissue homeostasis and, if sustained, can result in cartilage degradation and onset of osteoarthritis pathology. Enhanced dysregulation of PCM/ECM turnover is partially driven by mechanically mediated proteolytic degradation of cartilage ECM components. This generates bioactive breakdown fragments such as fibronectin, biglycan and lumican fragments, which can subsequently activate or inhibit additional signalling pathways including those involved in inflammation. Finally, we discuss how bidirectionality within the ECM is critically important in enabling the chondrocytes to synthesise and release PCM/ECM molecules, growth factors, pro-inflammatory cytokines and proteolytic enzymes, under a specified load, to influence PCM/ECM composition and mechanical properties in cartilage health and disease.

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Section: The Pericellular Matrix and Its Role In Chondrocyte Mechanotransductionsupporting

confidence: 81%

Section: The Pericellular Matrix and Its Role In Chondrocyte Mechanotransductionmentioning

confidence: 99%

Section: The Pericellular Matrix and Its Role In Chondrocyte Mechanotransductionmentioning

confidence: 99%

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Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage

Gilbert

Bonnet

Blain

2021

IJMS

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“…It may contribute to stabilizing the cartilage matrix in OA [43]. Decorin upregulation has been proposed as an attempt to reduce aggrecan fragmentation in post-traumatic OA, and decorin-based therapeutics have been suggested to attenuate OA progression [44]. Concerning biglycan, this extracellular matrix component contributes to the regulation of chondrogenesis and ECM turnover in OA [45].…”

Section: Discussionmentioning

confidence: 99%

Equine Mesenchymal Stem/Stromal Cells Freeze-Dried Secretome (Lyosecretome) for the Treatment of Musculoskeletal Diseases: Production Process Validation and Batch Release Test for Clinical Use

et al. 2021

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In the last decades, it has been demonstrated that the regenerative therapeutic efficacy of mesenchymal stromal cells is primarily due to the secretion of soluble factors and extracellular vesicles, collectively known as secretome. In this context, our work described the preparation and characterization of a freeze-dried secretome (Lyosecretome) from adipose tissue-derived mesenchymal stromal cells for the therapy of equine musculoskeletal disorder. An intraarticular injectable pharmaceutical powder has been formulated, and the technological process has been validated in an authorized facility for veterinary clinical-use medicinal production. Critical parameters for quality control and batch release have been identified regarding (i) physicochemical properties; (ii) extracellular vesicle morphology, size distribution, and surface biomarker; (iii) protein and lipid content; (iv) requirements for injectable pharmaceutical dosage forms such as sterility, bacterial endotoxin, and Mycoplasma; and (v) in vitro potency tests, as anti-elastase activity and proliferative activity on musculoskeletal cell lines (tenocytes and chondrocytes) and mesenchymal stromal cells. Finally, proteins putatively responsible for the biological effects have been identified by Lyosecretome proteomic investigation: IL10RA, MXRA5, RARRES2, and ANXA1 modulate the inflammatory process RARRES2, NOD1, SERPINE1, and SERPINB9 with antibacterial activity. The work provides a proof-of-concept for the manufacturing of clinical-grade equine freeze-dried secretome, and prototypes are now available for safety and efficacy clinical trials in the treatment of equine musculoskeletal diseases

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“…TIRF microscopy has also found use complementing other technologies, such as its use in guiding atomic force microscopy (AFM) in testing the biomechanical properties of the pericellular matrix of chondrocytes found in cartilages. Chery et al used TIRF microscopy to explore the pericellular matrix (PCM), a narrow, specialized band of ECM found around chondrocytes of cartilage [ 109 ]. Using TIRF to image collagen IV, the resultant images were used to guide mechanical testing of the PCM using AFM, demonstrating the use of TIRF microscopy as a guide for other methods of ECM characterization.…”

Section: Imaging the Ecm Components: Past Present And Future Challengesmentioning

confidence: 99%

Optical Microscopy and the Extracellular Matrix Structure: A Review

Poole

Mostaço-Guidolin

2021

Cells

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Biological tissues are not uniquely composed of cells. A substantial part of their volume is extracellular space, which is primarily filled by an intricate network of macromolecules constituting the extracellular matrix (ECM). The ECM serves as the scaffolding for tissues and organs throughout the body, playing an essential role in their structural and functional integrity. Understanding the intimate interaction between the cells and their structural microenvironment is central to our understanding of the factors driving the formation of normal versus remodelled tissue, including the processes involved in chronic fibrotic diseases. The visualization of the ECM is a key factor to track such changes successfully. This review is focused on presenting several optical imaging microscopy modalities used to characterize different ECM components. In this review, we describe and provide examples of applications of a vast gamut of microscopy techniques, such as widefield fluorescence, total internal reflection fluorescence, laser scanning confocal microscopy, multipoint/slit confocal microscopy, two-photon excited fluorescence (TPEF), second and third harmonic generation (SHG, THG), coherent anti-Stokes Raman scattering (CARS), fluorescence lifetime imaging microscopy (FLIM), structured illumination microscopy (SIM), stimulated emission depletion microscopy (STED), ground-state depletion microscopy (GSD), and photoactivated localization microscopy (PALM/fPALM), as well as their main advantages, limitations.

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Decorin regulates cartilage pericellular matrix micromechanobiology

Cited by 42 publications

References 100 publications

Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage

Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage

Equine Mesenchymal Stem/Stromal Cells Freeze-Dried Secretome (Lyosecretome) for the Treatment of Musculoskeletal Diseases: Production Process Validation and Batch Release Test for Clinical Use

Optical Microscopy and the Extracellular Matrix Structure: A Review

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