Adipose Tissue-Derived Adult Stem Cells
Richard K. Burt, Alberto M. Marmont in Stem Cell Therapy for Autoimmune Disease, 2019
The conditions that favor chondrogenesis include growth factors of the FGF and TGF family as well as physical conditions such as lowered oxygen tension and appropriate matrices that maintain cells in a rounded shape, as found in cartilage in vivo.44,48-50 When cultured in media containing fetal bovine serum, ascorbate 2- phosphate, dexamethasone, and transforming growth factor beta 1 (TGF-β1), and embedded in alginate matrix or grown in pellet culture, ADAS cells expressed molecules characteristic of the chondrocyte phenotype. The molecules expressed by ADAS cells included cartilage matrix molecules including collagen type II, VI, and chondroitin 4-sulfate, a primary component of aggrecan.18,38,46,47 Unlike mesenchymal stem cells, however, ADAS cells under chondrogenic conditions do not appear to express type X collagen, a marker of hypertrophic chondrocytes.44 The cultured adipose derived chondrocytes maintained their chondrocyte phenotype after being implanted subcutaneously in nude mice for 4 to 12 weeks.46 These findings indicated the potential of adipose tissue derived cells as a source of cells for cartilage tissue engineering.
Structure and Function of Cartilage
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi in Articular Cartilage, 2017
The aggregation of many proteoglycans (Figure 1.25) into large macromolecules is critical for proper functionality of cartilage tissue (Figure 1.26). The large size of this polymer mesh acts to immobilize and restrain it within the collagen network. Because of the strong negative charge, the matrix imbibes fluid, swelling the tissue to maintain equilibrium, also known as the Donnan effect. The swelling is balanced against the mechanical restraint of the collagen network (Maroudas 1976). While aggrecan is also located in other tissues, such as heart, brain, tendon, and intervertebral disc, production of aggrecan in the matrix is considered an important marker of chondrogenesis and is directly regulated by Sox9 (Sekiya et al. 2000). Autosomal recessive diseases of aggrecan, including spondyloepimetaphyseal dysplasia in humans (Tompson et al. 2009), nanomelia in chickens, and cartilage matrix deficiency in mice, result in chondrodysplasias.
Introduction and Review of Biological Background
Luke R. Bucci in Nutrition Applied to Injury Rehabilitation and Sports Medicine, 2020
Aggrecan is the new name for the archetypal PG subunit found in cartilage.79,83,87 Aggrecans form very large polymers of aggregating PGs (40 to 100 million Da or more) by binding to a very long hyaluronan molecule with link proteins. Aggrecan makes up 10% of the wet weight of cartilage and, by virtue of its high concentration of negative charges, is capable of binding large amounts of water. In vivo, aggrecan is underhydrated, which exerts a swelling effect in cartilage. Thus, aggrecan PG is the main contributor of compressive, load-bearing properties in cartilage. Aggrecan is space-filling in three dimensions and is intertwined among collagen fibrils in cartilage. The architecture of aggrecan begins with a single, long-chain hyaluronan molecule of 1 to 20 million Da. To this hyaluronan molecule, about 40 PG subunits are attached. Each PG subunit is composed of a large core protein (210,000 Da) with attached carbohydrates and GAGs. The amino terminus of core proteins is attached to hyaluronan by several specialized link proteins. A region of single or small chains of carbohydrate residues is attached to core protein, followed by a region rich in keratan sulfate GAGs. Finally, a region of chondroitin sulfate GAGs is found on core protein. GAGs are attached to core protein by a linker assembly of sugars bound to asparagine residues. Chondroitin sulfate chains are usually longer than keratan sulfate chains, so that a net effect of longer and longer GAG chains is found on the length of each core protein. Thus, each PG subunit resembles a bottle brush in appearance, well-designed to fill spaces.
Therapeutic nanocarriers comprising extracellular matrix-inspired peptides and polysaccharides
Published in Expert Opinion on Drug Delivery, 2021
Lucas C. Dunshee, Millicent O. Sullivan, Kristi L. Kiick
Perhaps more relevant to the treatment of RA and/or OA are the proteoglycans aggrecan and lubricin. Aggrecan is commonly known for being a major component of intraarticular cartilage as a biomechanical support macromolecule. It can interact with HA and form distinct aggregates with it. As such, aggrecan could be incorporated in nanocarriers in the same manner HA already is routinely used and potentially as a co-complexation agent. In contrast to aggrecan, lubricin is known as a lubricating proteoglycan because of its ability to limit protein and cell interactions. Therefore, it could be envisaged as a biomechanical supplement for intraarticular HA nanocarriers or perhaps as an anti-opsonization coating for nanocarriers that are delivered systemically (either passively delivered or targeted), such as in nanoparticle-based cancer treatments.
CircSCAPER knockdown attenuates IL-1β-induced chondrocyte injury by miR-127-5p/TLR4 axis in osteoarthritis
Published in Autoimmunity, 2022
Yuchang Zhang, Ping Zhao, Sen Li, Xiangqian Mu, Huaqi Wang
Chondrocytes are the main cell population of cartilage and engaged in the synthesis and degradation of ECM in cartilage [27]. Chondrocyte apoptosis has been revealed to be closely related to articular cartilage destruction and ECM degradation during the progression of OA [28]. Aggrecan is the core proteins of the ECM in articular cartilage [29]. MMP-13, an ECM-degrading enzyme, regulates tissue modelling and repair, overexpression of which can lead to pathological mutations through extreme ECM degradation [30]. During the progression of OA, tissues throughout the OA joint are involved in the inflammatory process [25]. IL-1β is a significant pro-inflammatory cytokine, which can induce chondrocyte apoptosis, cause ECM degradation and joint inflammation, thus making for the progression of OA [4, 31]. Recently, circSCAPER reversed IL-1β-evoked inhibition of growth and ECM degradation in chondrocytes, indicating the involvement of circSCAPER in OA process. Consistent with these findings, our study also found that circSCAPER was highly expressed in the OA cartilages and IL-1β-induced chondrocytes, and knockdown of circSCAPER suppressed the apoptosis and ECM degradation in chondrocytes. In addition, we also confirmed that the release of proinflammatory cytokines and oxidative damage caused by IL-1β in chondrocytes were attenuated by circSCAPER silencing. Thus, circSCAPER siRNA may be a new molecule that can be used to prevent OA progression.
Systemic drugs with impact on osteoarthritis
Published in Drug Metabolism Reviews, 2019
Dragos Apostu, Ondine Lucaciu, Alexandru Mester, Daniel Oltean-Dan, Mihaela Baciut, Grigore Baciut, Simion Bran, Florin Onisor, Andra Piciu, Roxana D. Pasca, Andrei Maxim, Horea Benea
Proteoglycans are produced by chondrocytes and represent between 10-20% of cartilage weight, providing the compressive strength of the articular cartilage (Bhosale and Richardson 2008). There are two main classes of proteoglycans: large aggregating proteoglycan monomers such as aggrecans or versican, and smaller proteoglycans such as decorin, biglycan, epiphycan, lumican and fibromodulin (Roughley 2001; Bhosale and Richardson 2008). The most common matrix molecule is the proteoglycan aggrecan, which forms macromolecular aggregates with hyaluronic acid (Poole et al. 2002). Aggrecan has in its structure glycosaminoglycan (GAG) side chains of chondroitin sulfate and keratin sulfate (Bhosale and Richardson 2008; Goldring 2012). The negatively charged chondroitin sulfate and keratin sulfate chains have the ability to bind water, thus creating a structure that provides good resistance for deformation and for compression (Poole et al. 2002; Bhosale and Richardson 2008; Titorencu et al. 2010).