Bisphosphonate rescues cartilage from trauma damage by promoting mechanical sensitivity and calcium signaling in chondrocytes Y. Zhou, M. Park, L. Wang,

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Bisphosphonate rescues cartilage from trauma damage by promoting mechanical sensitivity and calcium signaling in chondrocytes Y. Zhou, M. Park, L. Wang, X. Lu Osteoarthritis and Cartilage Volume 22, Pages S307-S308 (April 2014) DOI: 10.1016/j.joca.2014.02.571 Copyright © 2014 Terms and Conditions

Fig. 1 Continuous administration of zolendronic acid (ZA), an FDA approved bisphosphonate to treat bone loss, suppressed the development of post-traumatic OA in a DMM mouse model. A) Histological analysis showed minor cartilage degeneration in ZA treated mouse. B) Cartilage damage score of tibia and femur were much lower in drug treated group. Osteoarthritis and Cartilage 2014 22, S307-S308DOI: (10.1016/j.joca.2014.02.571) Copyright © 2014 Terms and Conditions

Fig. 2 ZA treatment could rescue the cartilage from serum-damage. (A-B) ZA treatment improved Young’s modulus and dynamic modulus after long-term culture. (C) GAG content of cartilage allografts was higher in ZA rescued group after 4 weeks culture. (p<0.05) (D) Responsive rate of spontaneous calcium signaling in chondrocytes were significantly higher in ZA treated group on days 2, 8, and 15 (after 1-week serum exposure); (E-F) Live/Dead staining images 23 days after serum damage showed fewer dead cells in ZA treated group. Osteoarthritis and Cartilage 2014 22, S307-S308DOI: (10.1016/j.joca.2014.02.571) Copyright © 2014 Terms and Conditions

Fig. 3 Presence of ZA promoted the beneficial effects of mechanical loading, but had no effects during static culture. (A) Young’s Modulus and (B) Dynamic Modulus of cartilage allografts at D3, 1wk, 2wk and 4wk in vitro culture. Osteoarthritis and Cartilage 2014 22, S307-S308DOI: (10.1016/j.joca.2014.02.571) Copyright © 2014 Terms and Conditions

Fig. 4 Live/Dead stain images of cartilage allografts after 4-week culture. (A-B) Static culture groups with or without ZA in medium. (C-D) Samples cultured with mechanical stimulation. (Scale bar = 50 μm) Osteoarthritis and Cartilage 2014 22, S307-S308DOI: (10.1016/j.joca.2014.02.571) Copyright © 2014 Terms and Conditions

Fig. 5 Biochemical content and gene expression levels of cartilage allografts cultured with mechanical stimulation. (A) GAG and (B) collagen content at day 30. Expression of (C) Type I Collagen, (D) Type II Collagen, and (E) Aggrecan genes at day 14. (p<0.01) Osteoarthritis and Cartilage 2014 22, S307-S308DOI: (10.1016/j.joca.2014.02.571) Copyright © 2014 Terms and Conditions