Perlecan: Roles in osteoarthritis and potential treating target

Zhao, Xiaoyan; Xie, Wenqing; Xiao, Wenfeng; Li, Heng-Zhen; Naranmandakh, Shinen; Bruyère, Olivier; Reginster, Jean-Yves; Li, Yusheng

doi:10.1016/j.lfs.2022.121190

Cited by 4 publications

(3 citation statements)

References 130 publications

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“…Perlecan is a prominent component of foetal rudiment cartilage stem cell niches, and it promotes the differentiation of chondroprogenitor stem cells with roles in diarthrodial joint development [ 165 , 271 ]. Perlecan is an early chondrogenic marker [ 154 , 157 , 272 ] and promotes the development of rudiment cartilage [ 273 ], a transient tissue that is eventually replaced by bone by endochondral ossification as part of the process of skeletogenesis and may have roles in cartilage repair processes in OA [ 151 , 159 , 274 , 275 ]. Perlecan sequesters a number of growth factors and has fundamental roles to play in the promotion of the proliferation and differentiation of many cell types to promote tissue development and repair in disease [ 172 ].…”

Section: Hs Interactive Proteinsmentioning

confidence: 99%

The Glycosaminoglycan Side Chains and Modular Core Proteins of Heparan Sulphate Proteoglycans and the Varied Ways They Provide Tissue Protection by Regulating Physiological Processes and Cellular Behaviour

Farrugia,

Melrose

2023

IJMS

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This review examines the roles of HS–proteoglycans (HS–PGs) in general, and, in particular, perlecan and syndecan as representative examples and their interactive ligands, which regulate physiological processes and cellular behavior in health and disease. HS–PGs are essential for the functional properties of tissues both in development and in the extracellular matrix (ECM) remodeling that occurs in response to trauma or disease. HS–PGs interact with a biodiverse range of chemokines, chemokine receptors, protease inhibitors, and growth factors in immune regulation, inflammation, ECM stabilization, and tissue protection. Some cell regulatory proteoglycan receptors are dually modified hybrid HS/CS proteoglycans (betaglycan, CD47). Neurexins provide synaptic stabilization, plasticity, and specificity of interaction, promoting neurotransduction, neurogenesis, and differentiation. Ternary complexes of glypican-1 and Robbo–Slit neuroregulatory proteins direct axonogenesis and neural network formation. Specific neurexin–neuroligin complexes stabilize synaptic interactions and neural activity. Disruption in these interactions leads to neurological deficits in disorders of functional cognitive decline. Interactions with HS–PGs also promote or inhibit tumor development. Thus, HS–PGs have complex and diverse regulatory roles in the physiological processes that regulate cellular behavior and the functional properties of normal and pathological tissues. Specialized HS–PGs, such as the neurexins, pikachurin, and Eyes-shut, provide synaptic stabilization and specificity of neural transduction and also stabilize the axenome primary cilium of phototoreceptors and ribbon synapse interactions with bipolar neurons of retinal neural networks, which are essential in ocular vision. Pikachurin and Eyes–Shut interactions with an α-dystroglycan stabilize the photoreceptor synapse. Novel regulatory roles for HS–PGs controlling cell behavior and tissue function are expected to continue to be uncovered in this fascinating class of proteoglycan.

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Section: Hs Interactive Proteinsmentioning

confidence: 99%

The Glycosaminoglycan Side Chains and Modular Core Proteins of Heparan Sulphate Proteoglycans and the Varied Ways They Provide Tissue Protection by Regulating Physiological Processes and Cellular Behaviour

Farrugia,

Melrose

2023

IJMS

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“… 107 Interest has been shown in the use of perlecan for the repair of articular cartilage. 26 , 27 , 177 Areas of chondroid dysplasia in experimental disc degeneration resemble rudiment cartilage morphology and composition apparently undergoing a repairative response. 68 Perlecan may thus promote IVD repair giving some credibility to its use in repair of hyaline cartilage.…”

Section: Introductionmentioning

confidence: 99%

Diverse and multifunctional roles for perlecan (HSPG2) in repair of the intervertebral disc

Melrose,

Guilak

2024

JOR Spine

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Perlecan is a widely distributed, modular, and multifunctional heparan sulfate proteoglycan, which facilitates cellular communication with the extracellular environment to promote tissue development, tissue homeostasis, and optimization of biomechanical tissue functions. Perlecan‐mediated osmotic mechanotransduction serves to regulate the metabolic activity of cells in tissues subjected to tension, compression, or shear. Perlecan interacts with a vast array of extracellular matrix (ECM) proteins through which it stabilizes tissues and regulates the proliferation or differentiation of resident cell populations. Here we examine the roles of the HS‐proteoglycan perlecan in the normal and destabilized intervertebral disc. The intervertebral disc cell has evolved to survive in a hostile weight bearing, acidic, low oxygen tension, and low nutrition environment, and perlecan provides cytoprotection, shields disc cells from excessive compressive forces, and sequesters a range of growth factors in the disc cell environment where they aid in cellular survival, proliferation, and differentiation. The cells in mechanically destabilized connective tissues attempt to re‐establish optimal tissue composition and tissue functional properties by changing the properties of their ECM, in the process of chondroid metaplasia. We explore the possibility that perlecan assists in these cell‐mediated tissue remodeling responses by regulating disc cell anabolism. Perlecan's mechano‐osmotic transductive property may be of potential therapeutic application.

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“…Osteoarthritis (OA) is a chronic pain disease with whole arthropathies such as synovitis, osteophyte formation etc [1][2][3][4] . OA showed the articular cartilage degeneration and persistent pain, causing disability, loss of function, decreased quality of life [5][6][7] . In OA, the destruction of articular cartilage is the most important change [8,9] .…”

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confidence: 99%

A Review on Phytopharmacological Properties of Caesalpinia crista

Niu¹,

Zhang²,

Wang³

et al. 2023

IJPS

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Influence of Curcumin on TGF-β/Smad/ADAMTS-7 and Cartilage Cells ProliferationTo explore the function of curcumin on the cartilage cells, the cell proliferation and apoptosis by transforming growth factor-beta/suppressor of mothers against decapentaplegic/a disintegrin and metalloproteinase with thrombospondin motifs-7 axis was the objective of the study. The cell viability was detected by cell counting kit-8. The expression of transforming growth factor-beta, suppressor of mothers against decapentaplegic protein, a disintegrin and metalloproteinase with thrombospondin motifs-7, caspase-9, B-cell lymphoma 2, Bcl-2-associated X protein was determined by Western blot. The cartilage cells were treated with 1 mmol/l sodium nitroprusside for 24 h. Then, the cells were treated with different concentration of curcumin for 24 h. We found that 1 μmol/l curcumin could recover the cartilage cells proliferation. The transforming growth factor-beta and suppressor of mothers against decapentaplegic protein show high expression and a disintegrin and metalloproteinase with thrombospondin motifs-7 was low in the curcumin treatment group. Meanwhile, the apoptosis pathway was also detected. The caspase-9 and B-cell lymphoma 2 was higher in the curcumin treatment group than without curcumin group. However, the Bcl-2-associated X protein was lower. The cell viability, a disintegrin and metalloproteinase with thrombospondin motifs-7, caspase-9, B-cell lymphoma 2 and Bcl-2-associated X proteins also show no changes with or without curcumin when the transforming growth factor-beta was inhibited. We found that a disintegrin and metalloproteinase with thrombospondin motifs-7 show over expression, the transforming growth factor-beta and suppressor of mothers against decapentaplegic protein show high expression in the curcumin treatment group, the cell viability, caspase-9, B-cell lymphoma 2 and Bcl-2-associated X proteins show no changes with or without curcumin. Curcumin can promote the cartilage cells proliferation via transforming growth factor-beta/suppressor of mothers against decapentaplegic/a disintegrin and metalloproteinase with thrombospondin motifs-7 axis and inhibit the cell apoptosis.

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Perlecan: Roles in osteoarthritis and potential treating target

Cited by 4 publications

References 130 publications

The Glycosaminoglycan Side Chains and Modular Core Proteins of Heparan Sulphate Proteoglycans and the Varied Ways They Provide Tissue Protection by Regulating Physiological Processes and Cellular Behaviour

The Glycosaminoglycan Side Chains and Modular Core Proteins of Heparan Sulphate Proteoglycans and the Varied Ways They Provide Tissue Protection by Regulating Physiological Processes and Cellular Behaviour

Diverse and multifunctional roles for perlecan (HSPG2) in repair of the intervertebral disc

A Review on Phytopharmacological Properties of Caesalpinia crista

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