Origin and function of cartilage stem/progenitor cells in osteoarthritis

Jiang, Yangzi; Tuan, Rocky S.

doi:10.1038/nrrheum.2014.200

Cited by 318 publications

(289 citation statements)

References 77 publications

(138 reference statements)

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“…29 In contrast to tissue culture experiments, the growth plate cartilage has long been considered difficult to target with drugs or antisense molecules because of its relative avascularity compared with the highly vascular liver and kidney. 31 However, our success with drug therapy in the growth plate 16,18 led us to ask whether ASOs with high-affinity nucleoside modifications 32 could be delivered to growth plate chondrocytes and reduce MT-COMP intracellular retention. Recent studies have shown that chemically modified ASOs can reduce mRNA targets efficiently in extra-hepatic tissues and show pharmacological benefits in disease models.…”

Section: Comp Aso1 Is Delivered To Growth Plate Chondrocytesmentioning

confidence: 99%

Antisense Reduction of Mutant COMP Reduces Growth Plate Chondrocyte Pathology

et al. 2017

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Mutations in cartilage oligomeric matrix protein cause pseudoachondroplasia, a severe disproportionate short stature disorder. Mutant cartilage oligomeric matrix protein produces massive intracellular retention of cartilage oligomeric matrix protein, stimulating ER and oxidative stresses and inflammation, culminating in post-natal loss of growth plate chondrocytes, which compromises linear bone growth. Treatments for pseudoachondroplasia are limited because cartilage is relatively avascular and considered inaccessible. Here we report successful delivery and treatment using antisense oligonucleotide technology in our transgenic pseudoachondroplasia mouse model. We demonstrate delivery of human cartilage oligomeric matrix protein-specific antisense oligonucleotides to cartilage and reduction of cartilage oligomeric matrix protein expression, which largely alleviates pseudoachondroplasia growth plate chondrocyte pathology. One antisense oligonucleotide reduced steady-state levels of cartilage oligomeric matrix protein mRNA and dampened intracellular retention of mutant cartilage oligomeric matrix protein, leading to a reduction of inflammatory markers and cell death and partial restoration of proliferation. This novel and exciting work demonstrates that antisense-based therapy is a viable approach for treating pseudoachondroplasia and other human cartilage disorders. INTRODUCTIONTreatments of skeletal dysplasia/dwarfing conditions, including pseudoachondroplasia (PSACH), are few and fraught with problems because of the inaccessibility of chondrocytes within the cartilage matrix and the relative avascular nature of the cartilage environment. PSACH is clinically characterized by disproportionate short stature, rhizomelic shortening of the long bones, brachydactyly, and extreme joint laxity. 1,2 Joint pain in childhood and osteoarthritis (OA) in early adulthood are the most debilitating features of PSACH; only symptomatic treatments are available and have limited efficacy. 2,3 The diagnosis is made between 2-3 years of age when linear growth slows and a waddling gait develops. 1,2 Because the diagnosis, in most cases, is made post-natally, treatments aimed at resolving the pathology will have to be started immediately after diagnosis.PSACH is caused by mutations in cartilage oligomeric matrix protein (COMP), a pentameric extracellular matrix (ECM) glycoprotein abundant in musculoskeletal tissues. 4,5 Functionally, COMP facilitates type II collagen fibril assembly, enhances chondrocyte attachment in vitro, and interacts with other ECM proteins, including type II and IX collagens, matrilin 3, and SPARC. [6][7][8][9][10][11][12] In contrast, mutations in COMP cause misfolding of the protein, preventing export from the chondrocyte and resulting in massive retention within the endoplasmic reticulum (ER). 10,[13][14][15] Although this finding has long been appreciated, there was little understanding of the pathologic molecular mechanisms, which are critical to develop mechanism-driven therapeutics. To circumvent this proble...

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Section: Comp Aso1 Is Delivered To Growth Plate Chondrocytesmentioning

confidence: 99%

Antisense Reduction of Mutant COMP Reduces Growth Plate Chondrocyte Pathology

et al. 2017

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“…CSPCs are multipotent stem cells and identify by expression of specific surface markers, ability to self-renew, and differentiate into three cell types such as adipocytes, osteoblasts, and chondrocytes [37,38]. These cells are great tools for cell-based cartilage repair [37,[39][40][41].…”

Section: Avian Cartilage Stem/progenitor Cellsmentioning

confidence: 99%

Concise Review: Avian Multipotent Stem Cells as a Novel Tool for Investigating Cell-Based Therapies

Farzaneh¹,

Farzaneh²,

Mozdziak³

2017

JDVAR

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The chick embryo is a favorite and great in vivo model, which has long been used in embryology, developmental biology and applied sciences. Also, chicken embryo is the accessible model for transplantation and tracking studies. Avian multipotent stem cells have the capability to self-renew and differentiate into a variety of cell types in vitro. Avian multipotent stem cells were successfully isolated from bone marrow (BM), metanephric tissue, lung, amniotic cells, cartilage, and other embryonic and adult tissues. Subsequent analysis was performed to evaluate these multipotent cells in vitro. Results of the present study strongly contribute to the information related to the ability of avian multipotent stem cells to differentiate into cells such as adipocytes, osteoblasts, chondrocytes, astrocytes, and other committed cells. Avian multipotent stem cells may provide a new source of avian-derived cell lines for basic research and potential therapeutic applications.

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“…In fact, tissue stem cells have now been considered as the key factor and even a target of various diseasecausing factors. 33 and the potential role of particular SNP in affecting stem cell characteristics and quality should thereby be kept aware. Particularly, we should keep being cautious when autologous stem cells are used for a disease obviously associated with certain SNPs, or allogeneic stem cells from a donor carrying with disease-causing or susceptible SNPs same as recipients are transplanted.…”

Section: Disease-causing or Susceptible Snps From Donors May Have Impmentioning

confidence: 99%