Aggrecan Hypomorphism Compromises Articular Cartilage Biomechanical Properties and Is Associated with Increased Incidence of Spontaneous Osteoarthritis

International Journal of Molecular Sciences
Paolo AlbertonAttila Aszodi

Abstract

The gene encoding the proteoglycan aggrecan (Agc1) is abundantly expressed in cartilage during development and adulthood, and the loss or diminished deposition of the protein results in a wide range of skeletal malformations. Furthermore, aggrecan degradation is a hallmark of cartilage degeneration occurring in osteoarthritis. In the present study, we investigated the consequences of a partial loss of aggrecan in the postnatal skeleton and in the articular cartilage of adult mice. We took advantage of the previously described Agc1tm(IRES-CreERT2) mouse line, which allows for conditional and timely-regulated deletion of floxed, cartilage-expressed genes. As previously reported, the introduction of the CreERT2 cassette in the 3'UTR causes a disruption of the normal expression of Agc1 resulting in a hypomorphic deposition of the protein. In homozygous mice, we observed a dwarf phenotype, which persisted throughout adulthood supporting the evidence that reduced aggrecan amount impairs skeletal growth. Homozygous mice exhibited reduced proteoglycan staining of the articular cartilage at 6 and 12 months of age, increased stiffening of the extracellular matrix at six months, and developed severe cartilage erosion by 12 months. The ost...Continue Reading

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Citations

Feb 23, 2020·Expert Review of Molecular Diagnostics·Silvia RavalliGiuseppe Musumeci
Dec 11, 2019·International Journal of Molecular Sciences·Susanne Grässel, Attila Aszodi
Oct 8, 2020·Advanced Healthcare Materials·Amelie ErbenMichael Heymann
Oct 29, 2020·Aging Cell·Taketo TaguchiVera Gorbunova
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Anna BarkovskayaValerie M Weaver
Nov 24, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Xiao-Shuang HuangYong-Hui Yang
Jul 20, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Greig CouasnayFlorent Elefteriou

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Methods Mentioned

BETA
atomic force microscopy
X-ray
AFM
PCR
ELISA

Software Mentioned

IT
JPK Data Processing
syngo Imaging XS - VA60B
ZEN
GraphPad Prism
Igor Pro
LightCycler 96

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