-
Osteoarthritis and Cartilage Aug 2021To delineate the activities of decorin and biglycan in the progression of post-traumatic osteoarthritis (PTOA).
OBJECTIVE
To delineate the activities of decorin and biglycan in the progression of post-traumatic osteoarthritis (PTOA).
DESIGN
Three-month-old inducible biglycan (Bgn) and decorin/biglycan compound (Dcn/Bgn) knockout mice were subjected to the destabilization of the medial meniscus (DMM) surgery to induce PTOA. The OA phenotype was evaluated by assessing joint structure and sulfated glycosaminoglycan (sGAG) staining via histology, surface collagen fibril nanostructure and calcium content via scanning electron microscopy, tissue modulus via atomic force microscopy-nanoindentation, as well as subchondral bone structure and meniscus ossification via micro-computed tomography. Outcomes were compared with previous findings in the inducible decorin (Dcn) knockout mice.
RESULTS
In the DMM model, Bgn mice developed similar degree of OA as the control (0.44 [-0.18 1.05] difference in modified Mankin score), different from the more severe OA phenotype observed in Dcn mice (1.38 [0.91 1.85] difference). Dcn/Bgn mice exhibited similar histological OA phenotype as Dcn mice (1.51 [0.97 2.04] difference vs control), including aggravated loss of sGAGs, salient surface fibrillation and formation of osteophyte. Meanwhile, Dcn/Bgn mice showed further cartilage thinning than Dcn mice, resulting in the exposure of underlying calcified tissues and aberrantly high surface modulus. Bgn and Dcn/Bgn mice developed altered subchondral trabecular bone structure in both Sham and DMM groups, while Dcn and control mice did not.
CONCLUSION
In PTOA, decorin plays a more crucial role than biglycan in regulating cartilage degeneration, while biglycan is more important in regulating subchondral bone structure. The two have distinct activities and modest synergy in the pathogenesis of PTOA.
Topics: Animals; Biglycan; Cancellous Bone; Cartilage, Articular; Decorin; Disease Models, Animal; Disease Progression; Menisci, Tibial; Mice, Knockout; Ossification, Heterotopic; Osteoarthritis; Osteophyte; Tibial Meniscus Injuries; Mice
PubMed: 33915295
DOI: 10.1016/j.joca.2021.03.019 -
Seminars in Cancer Biology May 2020The need for more effective cancer therapies is omnipresent as the ever-complex, and highly adaptive, mechanisms of tumor biology allow this disease to elude even the... (Review)
Review
The need for more effective cancer therapies is omnipresent as the ever-complex, and highly adaptive, mechanisms of tumor biology allow this disease to elude even the most stringent treatment options. The expanding field of proteoglycan signaling is enticing as a reservoir of potential drug targets and prospects for novel therapeutic strategies. The newest trend in proteoglycan biology is the interplay between extracellular signaling and autophagy fueled by the close link between autophagy and angiogenesis. Here we summarize the most current evidence surrounding proteoglycan signaling in both of these biological processes featuring the well-known suspects, decorin and perlecan, as well as other up-and-coming neophytes in this evolving signaling web.
Topics: Animals; Autophagy; Biomarkers; Decorin; Endothelial Cells; Humans; Neovascularization, Pathologic; Proteoglycans; Signal Transduction
PubMed: 31078640
DOI: 10.1016/j.semcancer.2019.05.003 -
Medical Hypotheses Jul 2021Coronavirus pandemic has emerged as an extraordinary healthcare crisis in modern times. The SARS-CoV-2 novel coronavirus has high transmission rate, is more aggressive...
Coronavirus pandemic has emerged as an extraordinary healthcare crisis in modern times. The SARS-CoV-2 novel coronavirus has high transmission rate, is more aggressive and virulent in comparison to previously known coronaviruses. It primarily attacks the respiratory system by inducing cytokine storm that causes systemic inflammation and pulmonary fibrosis. Decorin is a pluripotent molecule belonging to a leucine rich proteoglycan group that exerts critical role in extracellular matrix (ECM) assembly and regulates cell growth, adhesion, proliferation, inflammation, and fibrogenesis. Interestingly, decorin has potent anti-inflammatory, cytokine inhibitory, and anti-fibrillogenesis effects which make it a potential drug candidate against the COVID-19 related complications especially in the context of lung fibrosis. Herein, we postulate that owing to its distinctive pharmacological actions and immunomodulatory effect, decorin can be a promising preclinical therapeutic agent for the therapy of COVID-19.
Topics: COVID-19; Cytokines; Decorin; Humans; Pandemics; SARS-CoV-2
PubMed: 34098463
DOI: 10.1016/j.mehy.2021.110612 -
Ginekologia Polska 2020Preeclampsia (PE) is a pregnancy complication caused by typically limited proliferation, apoptosis, migration, and invasion of extra-trophoblast cells. Decorin (DCN) is...
OBJECTIVES
Preeclampsia (PE) is a pregnancy complication caused by typically limited proliferation, apoptosis, migration, and invasion of extra-trophoblast cells. Decorin (DCN) is a decidua-derived transforming growth factor (TGF)-binding proteoglycan which exerts multiple physiological functions such as collagen fibrillogenesis, myogenesis, angiostasis, and restraining placental invasiveness by adversely regulate proliferation, migration, and invasiveness of human extravillous trophoblast cells. Preeclampsia is mainly classified as early- and late-onset PE according to the timing of the disease onset. In the present study, we aimed to investigate the DCN levels in early-onset PE (EOPE, < 34 weeks) and late-onset severe PE (LOPE, ≥ 34 weeks) and uncomplicated pregnancies.
MATERIAL AND METHODS
In this case-control study, serum samples were obtained from 21 pregnant women with EOPE and 29 pregnant women with LOPE, as well as from 38 healthy controls (n = 12 early-onset controls and n = 26 late-onset controls) with uncomplicated pregnancies.
RESULTS
The mean DCN level was statistically significantly higher in the early-onset PE controls than late-onset PE controls (p = 0.040). Although the mean DCN level was higher in the early-onset PE controls than EOPE and LOPE groups, it did not reach statistical significance (p = 0.119 and p = 0.117, respectively).
CONCLUSIONS
Although DCN has been thought to play a role in the pathophysiology of PE, our study results show that DCN is not a useful predictive marker of EOPE and LOPE. Further large-scale studies are needed to draw a definitive conclusion.
Topics: Adolescent; Adult; Biomarkers; Case-Control Studies; Decorin; Female; Humans; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Trimesters; Prenatal Diagnosis; Prospective Studies; Young Adult
PubMed: 32495932
DOI: 10.5603/GP.2020.0050 -
Frontiers in Pharmacology 2019Healing of cutaneous wounds is a complex and well-coordinated process requiring cooperation among multiple cells from different lineages and delicately orchestrated... (Review)
Review
Healing of cutaneous wounds is a complex and well-coordinated process requiring cooperation among multiple cells from different lineages and delicately orchestrated signaling transduction of a diversity of growth factors, cytokines, and extracellular matrix (ECM) at the wound site. Most skin wound healing in adults is imperfect, characterized by scar formation which results in significant functional and psychological sequelae. Thus, the reconstruction of the damaged skin to its original state is of concern to doctors and scientists. Beyond the traditional treatments such as corticosteroid injection and radiation therapy, several growth factors or cytokines-based anti-scarring products are being or have been tested in clinical trials to optimize skin wound healing. Unfortunately, all have been unsatisfactory to date. Currently, accumulating evidence suggests that the ECM not only functions as the structural component of the tissue but also actively modulates signal transduction and regulates cellular behaviors, and thus, ECM should be considered as an alternative target for wound management pharmacotherapy. Of particular interest are small leucine-rich proteoglycans (SLRPs), a group of the ECM, which exist in a wide range of connecting tissues, including the skin. This manuscript summarizes the most current knowledge of SLRPs regarding their spatial-temporal expression in the skin, as well as lessons learned from the genetically modified animal models simulating human skin pathologies. In this review, particular focus is given on the diverse roles of SLRP in skin wound healing, such as anti-inflammation, pro-angiogenesis, pro-migration, pro-contraction, and orchestrate transforming growth factor (TGF)β signal transduction, since cumulative investigations have indicated their therapeutic potential on reducing scar formation in cutaneous wounds. By conducting this review, we intend to gain insight into the potential application of SLRPs in cutaneous wound healing management which may pave the way for the development of a new generation of pharmaceuticals to benefit the patients suffering from skin wounds and their sequelae.
PubMed: 32063855
DOI: 10.3389/fphar.2019.01649 -
Plastic and Reconstructive Surgery.... Apr 2022Variations in skin healing capacities are observed during different murine embryonic developmental stages. Through embryonic day 16 (E16), embryos are able to regenerate...
BACKGROUND
Variations in skin healing capacities are observed during different murine embryonic developmental stages. Through embryonic day 16 (E16), embryos are able to regenerate dermal architecture following flank skin wounding; however, after E17, wounds heal incompletely, inducing scar formation. The regenerative ability of the E16 fetal dermis depends on the migration of dermal mesenchymal cells. Decorin is a small molecule known to affect tissue tensile strength, cell phenotype, and tissue repair, including skin wound healing. In the current study, we evaluated the expression and roles of decorin in wound healing.
METHODS
Surgical injury was induced at E16 and E17 in ICR mouse embryos. Decorin expression was evaluated in tissue samples from these embryos using immunohistochemistry and reverse transcription quantitative polymerase chain reaction. Cell migration assays were used to evaluate wound healing capability of separated dermal and fascial tissues.
RESULTS
Our results showed that decorin exhibited distinct expression patterns during wound healing at E16 versus E17. Additionally, decorin expression altered cell migration in vitro. Dermal and fascial mesenchymal cells were found to exhibit distinct migration patterns concomitant with altered decorin expression. Specifically, decorin inhibited migration and favored scar formation.
CONCLUSION
Decorin expression may contribute to scar formation in the late stage of mouse embryos by inhibiting the migration of dermal mesenchymal cells.
PubMed: 35425688
DOI: 10.1097/GOX.0000000000004245 -
Reproductive Sciences (Thousand Oaks,... Jan 2021Preterm birth is a leading cause of infant morbidity and mortality. Decorin and biglycan are proteoglycans that play key roles in maintaining the connective tissue...
Preterm birth is a leading cause of infant morbidity and mortality. Decorin and biglycan are proteoglycans that play key roles in maintaining the connective tissue matrix and tensile strength of human fetal membranes and have been previously linked to PPROM. Extracellular matrix proteins, such as matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), TIMP metallopeptidase inhibitor 1 (TIMP-1), TIMP metallopeptidase inhibitor 2 (TIMP-2), and collagen VI (COL-6), have also been linked to PPROM and may have utility in a serum-based screening model for this condition. To define the natural course of serum decorin and biglycan expression throughout the duration of healthy pregnancy, to explore patterns of serum decorin and biglycan expression in serum of asymptomatic women who go on to develop spontaneous preterm labor, and to investigate the potential role for matrix metalloproteinases, their inhibitors, and collagen VI in a serum-based screening model to predict PPROM. Serum decorin level decreases less than 1% per week, and serum biglycan decreases by 2.9% per week over the duration of healthy pregnancy. Serum decorin and biglycan concentrations do not differ in spontaneous preterm labor cases compared with those in controls. Mean concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, and COL-6 do not differ in PPROM cases compared with those in controls. We have demonstrated that serum decorin and biglycan concentrations remain stable throughout the duration of normal pregnancy and are not early indicators of preterm labor, while common MMPs, TIMPs, and collagen VI are not early indicators of PPROM.
Topics: Biglycan; Biomarkers; Collagen Type VI; Decorin; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix Proteins; Female; Fetal Membranes, Premature Rupture; Humans; Matrix Metalloproteinases; Predictive Value of Tests; Pregnancy; Premature Birth; Retrospective Studies; Tissue Inhibitor of Metalloproteinases
PubMed: 32804350
DOI: 10.1007/s43032-020-00251-1 -
Frontiers in Oncology 2019The small leucine-rich proteoglycan (SLRP) family consists of 18 members categorized into five distinct classes, the traditional classes I-III, and the non-canonical... (Review)
Review
The small leucine-rich proteoglycan (SLRP) family consists of 18 members categorized into five distinct classes, the traditional classes I-III, and the non-canonical classes IV-V. Unlike the other class I SLRPs (decorin and biglycan), asporin contains a unique and conserved stretch of aspartate (D) residues in its N terminus, and germline polymorphisms in the D-repeat-length are associated with osteoarthritis and prostate cancer progression. Since the first discovery of asporin in 2001, previous studies have focused mainly on its roles in bone and joint diseases, including osteoarthritis, intervertebral disc degeneration and periodontal ligament mineralization. Recently, gene expression was also reported to be dysregulated in tumor tissues of different types of cancer, and to act as oncogene in pancreatic, colorectal, gastric, and prostate cancers, and some types of breast cancer, though it is also reported to function as a tumor suppressor gene in triple-negative breast cancer. Furthermore, asporin is also positively or negatively correlated with tumor proliferation, migration, invasion, and patient prognosis through its regulation of different signaling pathways, including the TGF-β, EGFR, and CD44 pathways. In this review, we seek to elucidate the signaling pathways and functions regulated by asporin in different types of cancer and to highlight some important issues that require investigation in future research.
PubMed: 31608236
DOI: 10.3389/fonc.2019.00948 -
American Journal of Physiology. Cell... Nov 2022Decorin, a small leucine-rich proteoglycan with multiple biological functions, is known to evoke autophagy and mitophagy in both endothelial and cancer cells. Here, we...
Decorin, a small leucine-rich proteoglycan with multiple biological functions, is known to evoke autophagy and mitophagy in both endothelial and cancer cells. Here, we investigated the effects of soluble decorin on mitochondrial homeostasis using live cell imaging and ex vivo angiogenic assays. We discovered that decorin triggers mitochondrial depolarization in triple-negative breast carcinoma, HeLa, and endothelial cells. This bioactivity was mediated by the protein core in a time- and dose-dependent manner and was specific for decorin insofar as biglycan, the closest homolog, failed to trigger depolarization. Mechanistically, we found that the bioactivity of decorin to promote depolarization required the MET receptor and its tyrosine kinase. Moreover, two mitochondrial interacting proteins, mitostatin and mitofusin 2, were essential for downstream decorin effects. Finally, we found that decorin relied on the canonical mitochondrial permeability transition pore to trigger tumor cell mitochondrial depolarization. Collectively, our study implicates decorin as a soluble outside-in regulator of mitochondrial dynamics.
Topics: Humans; Biglycan; Carcinoma; Decorin; Endothelial Cells; Extracellular Matrix Proteins; Mitochondrial Permeability Transition Pore; Protein-Tyrosine Kinases; Signal Transduction
PubMed: 36036446
DOI: 10.1152/ajpcell.00325.2022 -
Open Biology Jan 2022The extracellular matrix (ECM) exists as a dynamic network of biophysical and biochemical factors that maintain tissue homeostasis. Given its sensitivity to changes in... (Review)
Review
The extracellular matrix (ECM) exists as a dynamic network of biophysical and biochemical factors that maintain tissue homeostasis. Given its sensitivity to changes in the intra- and extracellular space, the plasticity of the ECM can be pathological in driving disease through aberrant matrix remodelling. In particular, cancer uses the matrix for its proliferation, angiogenesis, cellular reprogramming and metastatic spread. An emerging field of matrix biology focuses on proteoglycans that regulate autophagy, an intracellular process that plays both critical and contextual roles in cancer. Here, we review the most prominent autophagic modulators from the matrix and the current understanding of the cellular pathways and signalling cascades that mechanistically drive their autophagic function. We then critically assess how their autophagic functions influence tumorigenesis, emphasizing the complexities and stage-dependent nature of this relationship in cancer. We highlight novel emerging data on immunoglobulin-containing and proline-rich receptor-1, heparanase and thrombospondin 1 in autophagy and cancer. Finally, we further discuss the pro- and anti-autophagic modulators originating from the ECM, as well as how these proteoglycans and other matrix constituents specifically influence cancer progression.
Topics: Autophagy; Extracellular Matrix; Humans; Neoplasms; Neovascularization, Pathologic; Proteoglycans
PubMed: 34982945
DOI: 10.1098/rsob.210304