Recent Advances in Proteoglycans

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 3422

Special Issue Editor


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Guest Editor
School of Pharmacy, Chapman University, Orange, CA, USA
Interests: glycoproteins; inflammation; macrophages; extracellular matrix proteins

Special Issue Information

Dear Colleagues,

Proteoglycans are a ubiquitous family of heavily glycosylated proteins with distinct forms and functions. Over the past 20 years, advancements in elucidating various structural subtypes and identifying cellular locations of proteoglycans have led to the development of a complex classification system for proteoglycans. Proteoglycans can localize either intracellularly as components of secretory granules being anchored to the cell surface or by spanning the cell membrane in addition to being localized in the pericellular region as components of the basement membrane. The largest class of proteoglycans is, however, secreted into the extracellular space. These secreted proteoglycans are key structural components of cartilage, blood vessels, and the central nervous system and have the canonical role of maintaining the architecture of various tissues. In addition, secreted proteoglycans can interact with various receptors either as ligands or via their ability to interact with the natural ligands of these receptors, resulting in indirect regulation of receptor activation. The largest subclass of secreted proteoglycans is small leucine-rich proteoglycans (SLRPs), of which 5 classes have been characterized to date. SLRPs exhibit different biological functions, including control of cell growth and differentiation, modulation of transforming growth factor beta (TGF-b) signaling, and control of fibroblast differentiation and collagen fibrogenesis. Secreted proteoglycans also play a role in regulating inflammation and the immune system. Proteoglycans, e.g., biglycan and proteoglycan-4 (PRG4), are ligands for the toll-like receptors (TLR2 and TLR4), where they produce divergent biological effects. Soluble biglycan can activate TLR2 and TLR4, resulting in an acute inflammatory response, while PRG4 binds TLR2 and TLR4, resulting in inhibition of receptor activation by damage-associated molecular patterns (DAMPs).

In this Special Issue of Biomolecules, titled “Recent Advances in Proteoglycans”, we would like to present recent findings supporting the biological role of secreted proteoglycans in regulating cell growth, transformation, and tissue remodeling in diseases of chronic inflammation and associated tissue fibrosis in the context of innate and adaptive immune regulation.

Prof. Dr. Khaled A. Elsaid
Guest Editor

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Keywords

  • extracellular matrix
  • SLRPs
  • aggrecans
  • innate immunity
  • proteoglycans
  • toll-like receptor
  • fibrosis

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Published Papers (1 paper)

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Research

15 pages, 2287 KiB  
Article
Trabecular Bone Deficit and Enhanced Anabolic Response to Re-Ambulation after Disuse in Perlecan-Deficient Skeleton
by Ashutosh Parajuli, Shaopeng Pei, Hongbo Zhao, Jerahme R. Martinez, X. Lucas Lu, X. Sherry Liu, Mary C. Farach-Carson, Catherine B. Kirn-Safran and Liyun Wang
Biomolecules 2020, 10(2), 198; https://doi.org/10.3390/biom10020198 - 29 Jan 2020
Cited by 2 | Viewed by 2961
Abstract
Perlecan/Hspg2, a large monomeric heparan sulfate proteoglycan, is found in the basement membrane and extracellular matrix, where it acts as a matrix scaffold, growth factor depot, and tissue barrier. Perlecan deficiency leads to skeletal dysplasia in Schwartz-Jampel Syndrome (SJS) and is a risk [...] Read more.
Perlecan/Hspg2, a large monomeric heparan sulfate proteoglycan, is found in the basement membrane and extracellular matrix, where it acts as a matrix scaffold, growth factor depot, and tissue barrier. Perlecan deficiency leads to skeletal dysplasia in Schwartz-Jampel Syndrome (SJS) and is a risk factor for osteoporosis. In the SJS-mimicking murine model (Hypo), inferior cortical bone quality and impaired mechanotransduction in osteocytes were reported. This study focused on trabecular bone, where perlecan deficiency was hypothesized to result in structural deficit and altered response to disuse and re-loading. We compared the Hypo versus WT trabecular bone in both axial and appendicular skeletons of 8-38-week-old male mice, and observed severe trabecular deficit in Hypo mice, approximately 50% reduction of Tb.BV/TV regardless of skeletal site and animal age. Defects in endochondral ossification (e.g., accelerated mineralization), increases in osteoclast activity, and altered differentiation of bone progenitor cells in marrow contributed to the Hypo phenotype. The Hypo trabecular bone deteriorated further under three-week hindlimb suspension as did the WT. Re-ambulation partially recovered the lost trabecular bone in Hypo, but not in WT mice. The novel finding that low-impact loading could counter detrimental disuse effects in the perlecan-deficient skeleton suggests a strategy to maintain skeletal health in SJS patients. Full article
(This article belongs to the Special Issue Recent Advances in Proteoglycans)
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