Knockout of hyaluronidase Spam1 reduces age-related bone and cartilage changes in mouse knee

Abstract

Objective: To investigate the role of Spam1 hyaluronidase in age-related bone and cartilage changes in the mouse knee.

Design: Spam1^-/- and WT mice were euthanised at different ages from 10 to 52 weeks. The right hindlimbs were dissected, scanned with peripheral Quantitative Computed Tomography (pQCT) and then decalcified for histological analysis (modified Mankin score). In other mice, cartilages of both tibiae were sampled at 10, 30 and 52 weeks of age for RNA extraction and qPCR analysis. We assessed the expression of hyaluronidases Hyal1 and Hyal2, hyaluronan synthase HAS2, extracellular matrix proteases Mmp13 and Adamts-5, and type 2 collagen.

Results: Spam1^-/- mice did not exhibit specific morphological characters up to 52 weeks of age. From 20 weeks, the proximal tibia of Spam1^-/- mice had a significantly lower bone mineral density than WT mice. At 52 weeks, the modified Mankin score was significantly lower in Spam1^-/- than WT mice. Spam1^-/- chondrocytes expressed significantly less Hyal2 than WT ones at all ages and less Mmp13 at 52 weeks. Through all the experiment, the Hyal1 expression of Spam1^-/- chondrocytes remained similar as that of WT chondrocytes.

Conclusion: Spam1 knockout reduced significantly cartilage degradation in mouse knee whereas the chondrocyte expression of Hyal 1, Hyal 2 and Mmp13 was modified, suggesting a role of this hyaluronidase in cartilage metabolism.

Keywords: Ageing; Cartilage; Hyaluronidase; Spam1.