*4.1. Tibial Compression Overload Injury*

Right knee joints of 10-week-old and 62-week-old C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME, USA; Stock No: 000664) received a single non-invasive tibial compression overload at 1 mm/s displacement rate until ACL rupture using an electromagnetic material testing system (ElectroForce 3200, TA Instruments, New Castle, DE, USA), as previously described [8,10,19]. Buprenorphine was administered immediately post-injury (0.01 mg/kg) for pain relief. All animal experimental procedures were completed in accordance with the Institutional Animal Care and Use Committee (IACUC) guidance at Lawrence Livermore National Laboratory and the University of California, Davis in AAALAC-accredited facilities under protocol 168 approved in February 2019.
