Altered joint mechanics produced by periarticular bone remodelling may precede the cartilage changes of osteoarthritis (OA). Recently, receptor activator of nuclear factor kappa beta (RANK), along with its soluble ligand (RANK-L), have been shown to induce both maturation and activation of bone-degrading osteoclasts. Activation of RANK on osteoclast cells by RANK-L is opposed by another soluble factor, osteoprotegerin (OPG). Thus RANK/OPG balance is important in regulating bone turnover. Here, we compared periarticular bone from patients with end-stage OA undergoing total knee arthroplasty (TKA) with those of cadaveric controls. We assessed bony, histological and molecular changes that are important in the pathogenesis of OA. Using in-situ hybridization, we found increased staining of digoxygenase (DIG)-labelled OPG in osteoblasts of TKA bone. A corresponding increase in subchondral and insertional bone was seen on micro-CT (μCT) sections from TKA bone in comparison with cadaveric controls. Those changes were accompanied by marked articular cartilage degeneration on histology. This study is the first of which we are aware that directly assessed the role of OPG in inducing the bony changes seen in human end-stage OA. We used μCT to compare corresponding samples qualitatively from TKA and cadaveric bone. Adjacent sections underwent hybridization of digoxygenase (DIG)-labelled OPG riboprobes to assess gene expression in situ. Finally, samples were stained and analysed for histology. Bony hypertrophy may be a result of overexpression of OPG that occurs as an important feature of OA pathophysiology. Funding: This work was supported by a grant from the Hip Hip Hooray Fund of the Canadian Orthopaedic Research Foundation (CORF) and the Wood Professorship in Joint Injury Research. There was no commercial funding for this research project.
Ten New Zealand White rabbits underwent anterior cruciate ligament transection (ACLX), then reconstruction using a mersiline tape graft and mitek mini anchors. Animals were divided into two groups and sacrificed at six and fourteen week after surgery. Medial collateral ligament (MCL)-complexes were evaluated for joint laxity, and periarticular tissues evaluated for changes in vascular volume. Both reconstructed groups showed significantly reduced MCL-complex laxity and inflammatory angiogenesis compared to ACLX controls. This reconstructive method (using an artificial graft) provided transient restabilization out to 6 and 14 wk after ACLX in the rabbit, with a high 80% success rate of intact grafts. To refine a method of ACL reconstruction in the New Zealand White (NZW) rabbit to study angiogenic adaptations in a restabilized knee joint. The artificial graft approach provided transient restabilization out to six and fourteen week post ACLX with an 80% success rate, and reduced MCL-complex laxity and inflammatory angiogenesis. Addressing joint instability after ACLX reduces inflammatory angiogenesis and mechanical deterioration in peri-articular tissues, and delays the progression of OA. Compared to normal control tissues, loss of the ACL resulted in marked joint instability, and significantly increased vascular volumes in all periarticular tissues examined six and fourteen week post-ACLX. However, following transient restabilization using reconstructive surgery, MCL-complex laxity and periarticular tissue vascular volume were significantly reduced at both the six and fourteen week intervals compared to ACLX controls. ACL reconstructive surgery was performed on the right knee of ten skeletally mature NZW rabbits using a mersiline tape graft and mitek mini anchors, immediately after the ACL had been transected. MCL-complex laxity was measured in all joints using established biomechanical procedures. To assess the effect of joint restabilization six and fourteen week after ACL reconstruction, limbs were infused with a 5% carmine red dye/5% gelatin solution, and the vascular volume of periarticular tissues was detemined. The artificial graft approach to rabbit ACL reconstruction resulted in a high success rate of intact grafts 6 and 14 wk post-ACLX. The transient restabilization of an ACLX knee joint results in less inflammatory angio-genesis in periarticular tissues.
