Background/Purpose: In articular (AC) and growth plate (GP) cartilage, the small leucine-rich proteoglycan decorin is mainly present within the interterritorial regions (ITs) of the extracellular matrix. Within the extracellular matrix it is associated with thick, well-banded collagen fibrils. Here we analyzed the impact of decorin‑deficiency (Dcn^-/-) on the biomechanical properties of cartilage and the development of osteoarthritis via forced exercise.

Methods: Diverse cartilaginous tissues of Dcn^-/- mice and wild-type (WT) mice were examined at different developmental time points by histology/immunohistochemistry and by atomic force microscopy (AFM). The levels of active TGF-β were analyzed by ELISA. Expression of glycosaminoglycan (GAG) modifing enzymes was assesed via semi-quantitave RT-PCR. Osteoarthritic changes (OA) were induced in 3 month-old Dcn^-/- and WT mice via forced running on a treadmill. The severity of the disease was evaluated via a modified Mankin score.

Results: In P14.5 and adult Dcn^-/- mice, Alcian blue (pH 1.0) stained highly sulfated GAGs intensely throughout the entire GP and AC. In WT mice, staining was weaker and mainly restricted to the pericellular/territorial zones. Likewise, antibodies to stubs of chondrotin-4-sulfate (DC4S) chains intensely labeled all zones of GP and AC in Dcn^-/- but not in WT mice. Futhermore, mutant mice showed an increased expression of enzymes involved in GAG modification (PAPSS1, C4ST2). By contrast, the distribution and staining intensities of core proteins like aggrecan or biglycan were similar in both genotypes. AFM analysis of AC sections at 3 months of age revealed slightly altered fibril architecture and increased compressive stiffness of the ITs from Dcn^-/- mice. Those abnormalities were accompanied by enhanced levels of TGF-β in mutant mice. Both genotypes exhibited osteoarthritic changes in knee joint cartilage after six weeks of forced running. However, the changes were less severe in Dcn^-/- than in WT mice (Mankin score 4.5 versus 6.5).

Conclusion: We propose the following mechanism attenuating OA in Dcn^-/- mice: Reportedly, decorin sequesters the cytokine TGF-β in the extracellular matrix. Higher levels of active TGF-β in cartilage of Dcn^-/- mice are likely to prevent inappropriate chondrocyte hypertrophy and, hence, induction of osteoarthritis. TGF-β is also known to affect sulfation of GAGs. Probably an increased sulfation leads to an augmented immobilization of water, increased osmotic swelling pressure and accordingly a stiffer cartilage matrix. Therefore, Dcn^-/- mice are less prone to develop osteoarthritis due to a combination of elevated active TGF-β levels and enhanced compressive stiffness of the articular cartilage.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/decorin-deficiency-alters-cartilage-stiffness-and-attenuates-the-development-of-osteoarthritis-in-mice/