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Article

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

1
Laboratory of Experimental Surgery and Regenerative Medicine, Clinic for General, Trauma and Reconstructive Surgery, Ludwig-Maximilians University, 80336 Munich, Germany
2
Center for Applied Tissue Engineering and Regenerative Medicine, Munich University of Applied Sciences, 80533 Munich, Germany
3
Center for NanoScience, Ludwig-Maximilians University Munich, 80799 Munich, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(5), 1008; https://doi.org/10.3390/ijms20051008
Received: 1 February 2019 / Revised: 18 February 2019 / Accepted: 21 February 2019 / Published: 26 February 2019
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 osteoarthritis in the hypomorph mice was not accompanied by increased expression of catabolic enzymes and matrix degradation neoepitopes. These findings suggest that the degeneration found in homozygous mice is likely due to the compromised mechanical properties of the cartilage tissue upon aggrecan reduction. View Full-Text
Keywords: aggrecan; articular cartilage; osteoarthritis; atomic force microscopy aggrecan; articular cartilage; osteoarthritis; atomic force microscopy
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MDPI and ACS Style

Alberton, P.; Dugonitsch, H.C.; Hartmann, B.; Li, P.; Farkas, Z.; Saller, M.M.; Clausen-Schaumann, H.; Aszodi, A. Aggrecan Hypomorphism Compromises Articular Cartilage Biomechanical Properties and Is Associated with Increased Incidence of Spontaneous Osteoarthritis. Int. J. Mol. Sci. 2019, 20, 1008. https://doi.org/10.3390/ijms20051008

AMA Style

Alberton P, Dugonitsch HC, Hartmann B, Li P, Farkas Z, Saller MM, Clausen-Schaumann H, Aszodi A. Aggrecan Hypomorphism Compromises Articular Cartilage Biomechanical Properties and Is Associated with Increased Incidence of Spontaneous Osteoarthritis. International Journal of Molecular Sciences. 2019; 20(5):1008. https://doi.org/10.3390/ijms20051008

Chicago/Turabian Style

Alberton, Paolo, Hans C. Dugonitsch, Bastian Hartmann, Ping Li, Zsuzsanna Farkas, Maximilian M. Saller, Hauke Clausen-Schaumann, and Attila Aszodi. 2019. "Aggrecan Hypomorphism Compromises Articular Cartilage Biomechanical Properties and Is Associated with Increased Incidence of Spontaneous Osteoarthritis" International Journal of Molecular Sciences 20, no. 5: 1008. https://doi.org/10.3390/ijms20051008

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