Characterization of the Subchondral Bone and Pain Behavior Changes in a Novel Bipedal Standing Mouse Model of Facet Joint Osteoarthritis

Abstract

Background. The subchondral bone parallels with the progression of osteoarthritis (OA). However, the biomechanical properties and histopathological changes of subchondral bone changes in the lumbar facet joint (LFJ) after long-term axial loading on the spine have not been explored. In this study, we aimed to investigate the subchondral bone histopathological changes that occur in the LFJ and pain behaviors in a novel bipedal standing mouse model. Methods. Sixteen 8-week-old male C57BL/6 mice were randomly assigned into bipedal standing and control groups. A finite element stimulate model based on the micro-CT data was generated to simulate the von Mises stress distribution on the LFJ during different positions. The spine pain behaviors tests were analysis. In addition, the change in the subchondral bone of the LFJ was assessed by histological and immunohistochemistry staining. Results. The computerized simulation of the von Mises stress distribution in the superior articular process of LFJ at the spine level 5 in the lying position increased and reached a maximum value at the bipedal standing posture. The spine pain behavior test revealed that the threshold of pressure tolerance decreased significantly in bipedal groups relative to control groups, whereas the mechanical hyperalgesia of the hind paw increased significantly in bipedal groups relative to control groups. The axial load accelerates LFJ degeneration with increased histological scores in bipedal groups. The expression of type II collagen and aggrecan (ACAN) was significantly decreased in the bipedal groups compared with the control groups, whereas the expression of MMP13 was increased. Compared with the control groups, the osteoclast activity was activated with higher TRAP-positive staining and associated with increased CD-31-positive vessels and GCRP-positive nerve ending expression in the subchondral bone of LFJ. Conclusion. Collectively, long-term axial loading induces the development of spine hyperalgesia in mice associate with increased osteoclast activity and aberrant angiogenesis and nerve invasion into the subchondral bone of LFJ that stimulates the natural pathological change in human LFJ OA. These results indicate that aberrant bone remodeling associate with aberrant nerve innervation in the subchondral bone has a potential as a therapeutic target in LFJ OA pain.

Mechanical overloading-induced miR-325-3p reduction promoted chondrocyte senescence and exacerbated facet joint degeneration

“…1 D–G). We further investigated whether cellular senescence also exists in degenerated FJ in mice, we induced FJ degeneration in mice using a bipedal standing model, which significantly increased spinal axial stress, as previously described [ 12 ]. We found that there was no significant difference in the facet joint degeneration of both sides of the standing model mice by HE staining and safranin O staining (Fig.…”

Facet joint degeneration—An initial procedure of the cervical spine degeneration

“…Progressive cartilage degeneration and pain hypersensitivity were observed. Miao Li et al 30 placed the mice in a beaker containing limited water to induce the bipedal standing posture and the LFJ OA was observed at 24 weeks. Due to the differences in anatomy, as described previously, the conclusions of these models do not apply to the cervical spine, and changes in the IVDs of the same segment have not been observed.…”

Long-term whole-body vibration induces degeneration of intervertebral disc and facet joint in a bipedal mouse model

“…Therefore, it is necessary to establish a novel animal model to simulate the daily posture of humans to establish the biomechanical loading conditions, because it is an essential step in the effort to explore the pathological changes of FJ degeneration associated with mechanical stress. Here, the current study uses a novel bipedal mouse model, which could simulate human standing postures for a long time (Ao et al, 2019;Li et al, 2020). Using this novel model provides natural positions resembling human beings, and gives researchers a chance to simulate the mechanical loadings in animal studies.…”

“…Thus, it is important to use a bipedal animal model to mimic the standing posture of humans as well as investigate the effects of high-frequency WBV conditions on IVD and FJ. Previous studies demonstrated a novel bipedal mouse model by placing mice in limited water to induce a standing posture for longperiods, and thus directly resulting in IVDD and FJ degeneration (Ao et al, 2019;Li et al, 2020). Here, the aim of the present study is to explore the effects of long-term WBV on the catabolic and anabolic metabolism of IVD and FJ using the novel bipedal mouse model.…”

“…As the disc height decreases due to IVDD, the load-bearing role of FJs increases (Dunlop et al, 1984;Schmidt et al, 2007;Schmidt et al, 2008). Similarly, the IVD benefits from the effects of FJ on limiting motion and thereby decreasing the strain on NP and AF (Ao et al, 2019;Li et al, 2020). Thus, it is important to use a bipedal animal model to mimic the standing posture of humans as well as investigate the effects of high-frequency WBV conditions on IVD and FJ.…”