Engineering osteoarthritic cartilage model through differentiating senescent human mesenchymal stem cells for testing disease-modifying drugs.

Science China. Life Sciences
Ning WangHang Lin

Abstract

Significant cellular senescence has been observed in cartilage harvested from patients with osteoarthritis (OA). In this study, we aim to develop a senescence-relevant OA-like cartilage model for developing disease-modifying OA drugs (DMOADs). Specifically, human bone marrow-derived mesenchymal stromal cells (MSCs) were expanded in vitro up to passage 10 (P10-MSCs). Following their senescent phenotype formation, P10-MSCs were subjected to pellet culture in chondrogenic medium. Results from qRT-PCR, histology, and immunostaining indicated that cartilage generated from P10-MSCs displayed both senescent and OA-like phenotypes without using other OA-inducing agents, when compared to that from normal passage 4 (P4)-MSCs. Interestingly, the same gene expression differences observed between P4-MSCs and P10-MSC-derived cartilage tissues were also observed between the preserved and damaged OA cartilage regions taken from human samples, as demonstrated by RNA Sequencing data and other analysis methods. Lastly, the utility of this senescence-initiated OA-like cartilage model in drug development was assessed by testing several potential DMOADs and senolytics. The results suggest that pre-existing cellular senescence can induce the generati...Continue Reading

References

Sep 1, 1990·Annals of the Rheumatic Diseases·C I WestacottP A Dieppe
Aug 12, 1999·Zeitschrift für Rheumatologie·J T Dingle
Apr 3, 2001·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·J A Martin, J A Buckwalter
Mar 29, 2002·Arthritis and Rheumatism·Sonsoles Piera-VelazquezDavidG Stokes
Sep 19, 2002·Biogerontology·James A Martin, Joseph A Buckwalter
May 2, 2003·The Journal of Bone and Joint Surgery. American Volume·James A Martin, Joseph A Buckwalter
Jul 29, 2003·Aging Cell·Jo S PriceIan M Clark
Dec 8, 2004·Experimental Gerontology·Barbara HampelPidder Jansen-Dürr
Aug 21, 2008·Nature Protocols·Marjolaine GossetClaire Jacques
Mar 7, 2012·Arthritis and Rheumatism·Richard F LoeserMary B Goldring
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Jan 15, 2013·Rheumatic Diseases Clinics of North America·Tuhina Neogi, Yuqing Zhang
Apr 12, 2013·Journal of Tissue Engineering and Regenerative Medicine·Alessandro BertoloJivko V Stoyanov
Apr 4, 2014·Bioinformatics·Anthony M BolgerBjoern Usadel
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
Dec 15, 2015·Cancer Discovery·Charles J SherrGeoffrey I Shapiro
Feb 3, 2016·The Veterinary Journal·Craig I JohnsonDylan N Clements
May 20, 2016·Nature Reviews. Rheumatology·Richard F LoeserBrian O Diekman
Jan 27, 2017·Aging Cell·Kendal McCullochTaranjit Singh Rai
Feb 23, 2017·Carbohydrate Polymers·Honghyun ParkKuen Yong Lee
May 19, 2017·Tissue Engineering. Part B, Reviews·Marta A SzychlinskaGiuseppe Musumeci
May 13, 2018·Stem Cell Research & Therapy·Yueh-Hsun Kevin YangGilda A Barabino
Jul 10, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nguyen P T HuynhFarshid Guilak
Aug 15, 2018·Mechanisms of Ageing and Development·Angyang HouJiang Peng
Nov 6, 2018·Osteoarthritis and Cartilage·P J CopeM Sharif
Dec 12, 2018·Best Practice & Research. Clinical Rheumatology·Terence W O'NeillJohn McBeth
Dec 18, 2018·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Gongming GaoWeimin Fan

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.