Structure and Function of Cartilage
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi in Articular Cartilage, 2017
Decorin and biglycan belong to the Class I SLRPs. Decorin, the most abundant SLRP in cartilage, is localized to the interterritorial matrix, with concentrations of decorin increasing with age (Roughley et al. 1994). The structure of decorin is semicircular with one dermatan or chondroitin sulfate attached. This concave structure supports its proposed function in associating with the collagen triple helix during fibril formation and regulating fibril spacing, as decorin has been observed “decorating” type II collagen fibrils. Interestingly, although decorin knockout mice have reduced tendon and skin tensile properties, resulting in skin fragility, the articular cartilage in adult mice appears normal (Reed and Iozzo 2002). Biglycan is localized to the pericellular matrix, with two dermatan or chondroitin sulfates attached. It is a regulator of bone formation, as biglycan knockout mice experience retarded skeletal growth (Young et al. 2002). Interestingly, both decorin and biglycan bind TGF-β. Fibromodulin, lumican, and prolargin belong to the Class II SLRPs, with both fibromodulin and lumican increasing in concentration with age. All three SLRPs bind to collagens. Fibromodulin has been linked to regulation of collagen fibril diameter (Hedbom and Heinegard 1989; Hedlund et al. 1994). The Class III SLRP epiphycan is found in the growth plate (Johnson et al. 1997).
Cell and Extracellular Matrix Interactions in a Dynamic Biomechanical Environment:
Michel R. Labrosse in Cardiovascular Mechanics, 2018
Proteoglycan content increases in diseased valves and is present in all layers (Hinton et al. 2006). The proteoglycans biglycan and decorin colocalize with apolipoproteins (O’Brien 1995) and retain low-density lipoproteins through electrostatic interactions (Neufeld et al. 2014). Biglycan and decorin have a higher expression in early lesions than in mature lesions (Stephens et al. 2011), and it has been suggested that their lipid and growth factor retention properties help promote lesion progression (Grande-Allen et al. 2007). The proteoglycans biglycan and decorin are known to bind and regulate the availability of TGF-β1 (Macri et al. 2007). Supportive of that theory, a study of a porcine model of early disease suggests that the development of proteoglycan-rich onlays in the fibrosa between the endothelial layer and elastic lamina may be one of the earliest events in CAVD occurring before significant lipid accumulation, inflammatory cell infiltration, or myofibroblast activation (Sider et al. 2014).
Metabolic bone disease
Philip E. Harris, Pierre-Marc G. Bouloux in Endocrinology in Clinical Practice, 2014
Bone is a vascularized skeletal tissue made up of an organic matrix, a mineral phase (calcium hydroxyapatite), and bone cells (osteoclasts, osteoblasts, and osteocytes). The organic matrix is composed of fibers of collagen (chiefly type 1 collagen); elastin and other proteins, such as osteocalcin and matrix Gla proteins; the Arg-Gly-Asp (RGD)-containing proteins, such as fibronectins, thrombospondins, vitronectin, fibrillin, osteopontin, and bone sialoprotein. Other noncollagen proteins of bone include osteonectin and tetranectin. Glycosaminoglycan (GAG)–containing proteins include biglycan, decorin, fibromodulin, and osteoadherin. Apart from its ability to provide structural integrity, bone has several biochemical functions, with bone itself serving as a calcium reservoir and its marrow as a hematopoietic organ. Bone formation by osteoblasts has two phases: synthesis of the bone matrix, including the formation of a network of collagenous fibers, and mineralization of the matrix. Osteoclasts, in contrast, bring about bone resorption, which also consists of two simultaneous processes: dissolution of hydroxyapatite crystals and proteolysis of the matrix. Anatomically, bone can be divided into cortical (compact) and trabecular (spongy, cancellous) parts. In trabecular bone, the interconnecting trabecular structures increase resistance to mechanical load.
The tumor microenvironment and triple-negative breast cancer aggressiveness: shedding light on mechanisms and targeting
Published in Expert Opinion on Therapeutic Targets, 2022
Natsuki Furukawa, Vered Stearns, Cesar A. Santa-Maria, Aleksander S. Popel
Biglycan (BGN) is a ubiquitously expressed proteoglycan that acts as a structural component of the extracellular matrix. Upon tissue damage, BGN gets cleaved and released from the ECM and initiates innate immunity reactions by acting as damage-associated molecular patterns (DAMPs) [128]. In TNBC, high expression of BGN is specifically seen in CAFs and differentiated perivascular-like (PVL) subpopulations. High expression of BGN associates with lower infiltration of CD8+ T cells and poor prognosis [129]. Knockout of BGN in the E0771 TNBC murine model led to the normalization of vasculature, improved delivery of chemotherapy, and increased infiltration of CD8+ T cells, indicating that BGN deteriorates the TME to an unfavorable environment [130]. CXCL16 is another molecule secreted by CAFs in TNBC. CXCL16 recruits myeloid cells into the TME of TNBC, which secrete immunosuppressive factors such as S100A9. The recruited myeloid cells further activate CAFs and induce expression of CXCL16, which creates a malignant positive feedback loop to form an immunosuppressive TME [131]. siRNA kinome screening identified PIK3Cδ in CAFs as an important factor that induced invasion of TNBC cells when cocultured with CAFs. Treatment of CAFs with the PIK3Cδ inhibitor CAL-101 altered the secretome of CAFs and induced the secretion of placental growth factor (PLGF) and brain-derived neurotrophic factor (BDNF). These proteins promoted the expression of nuclear receptor subfamily 4 group A (NR4A1), which is a tumor suppressor, in TNBC cells to inhibit invasion [132].
Landscape of cancer-associated fibroblasts identifies the secreted biglycan as a protumor and immunosuppressive factor in triple-negative breast cancer
Published in OncoImmunology, 2022
Shaoquan Zheng, Yutian Zou, Yuhui Tang, Anli Yang, Jie-Ying Liang, Linyu Wu, Wenwen Tian, Weikai Xiao, Xinhua Xie, Lu Yang, Jindong Xie, Weidong Wei, Xiaoming Xie
In this study, we explored the relative infiltration level of fibroblasts in triple-negative breast cancer and the correlation between CAFs and immune components in the TME. We further identified an upregulated secreted protein, biglycan, in CAFs compared with normal cancer-adjacent fibroblasts (NAFs) using RNA sequencing and mass spectrometry methods. Biglycan is encoded by the BGN gene and is mainly expressed in the stromal part of tumors. Biglycan is a protein that belongs to the small leucine-rich proteoglycan (SLRP) family. We found that the expression level of BGN is correlated with the extracellular matrix, lymphangiogenesis, epithelial-mesenchymal transition, angiogenesis and TGF-β signaling. Single-cell sequencing results show that BGN is mainly expressed in stromal fibroblasts. Moreover, BGN is highly expressed in CAFs of TNBC compared with other cell subpopulations. The role of BGN in the TME and its mechanism underlying how to affect the microenvironment remain unknown.
Serum endocan levels, carotid intima-media thickness and microalbuminuria in patients with newly diagnosed hypertension
Published in Clinical and Experimental Hypertension, 2019
Sevil Fisekci Oktar, Ibrahim Guney, Sayeste Akkan Eren, Levent Oktar, Kenan Kosar, Zafer Buyukterzi, Ender Alkan, Zeynep Biyik, Said Sami Erdem
Atherosclerosis results from a chronic, progressive inflammatory process associated with endothelial dysfunction as the incipient lesion, and progresses to an increased risk for thrombotic events (1). Endothelial dysfunction, atherosclerosis and hypertension (HT) are related with one another (2). Also, diffuse intimal thickening with an increase in proteoglycan content occurs prior to the influx of inflammatory cells. There are a number of different proteoglycans present in the vascular wall, one of which biglycan, which organizes and maintains the architecture of extracellular matrix (ECM) (3). Biglycan is released from the ECM during tissue injury and affects several biologic processes that are modulated by growth factors, cytokine functions, and the inflammatory response (4). One of the other proteoglycans is endocan.
Related Knowledge Centers
- Bone
- Cartilage
- Chondroitin Sulfate
- Dermatan Sulfate
- Glycosaminoglycan
- Proteoglycan
- Tendon
- X Chromosome
- Leucine-Rich Repeat
- Gene