Unilateral Osteotomy of Lumbar Facet Joint Induces a Mouse Model of Lumbar Facet Joint Osteoarthritis

Abstract

Study Design. The lumbar facet joint (LFJ) osteoarthritis (OA) model that highly mimics the clinical conditions was established and evaluated. Objective. Here, we innovatively constructed and evaluated the aberrant mechanical loading-related LFJ OA model. Summary of Background Data. LFJ is the only true synovial joint in a functional spinal unit in mammals. The LFJ osteoarthritis is considered to contribute 15% to 45% of low back pain. The establish of animal models highly mimicking the clinical conditions is a useful tool for the investigation of LFJ OA. However, the previously established animal models damaged the LFJ structure directly, which did not demonstrate the effect of aberrant mechanical loading on the development of LFJ osteoarthritis. Methods. In the present study, an animal model for LFJ degeneration was established by the unilateral osteotomy of LFJ (OLFJ) in L4/5 unit to induce the spine instability. Then, the change of contralateral LFJ was evaluated by morphological and molecular biological techniques. Results. We showed that the OLFJ induced instability accelerated the cartilage degeneration of the contralateral LFJ. Importantly, the SRμCT elucidated that the three-dimensional structure of the subchondral bone changed in contralateral LFJ, indicated as the abnormity of bone volume/total volume ratio (BV/TV), trabecular pattern factor (Tb. Pf), and the trabecular thickness (Tb. Th). Immunostaining further demonstrated the uncoupled osteoclastic bone resorption, and bone formation in the subchondral bone of contralateral LFJ, indicated as increased activity of osteoclast, osteoblast, and Type H vessels. Conclusion. We develop a novel LFJ OA model demonstrating the effect of abnormal mechanical instability on the degeneration of LFJ. This LFJ degeneration model that highly mimics the clinical conditions is a valuable tool to investigate the LFJ osteoarthritis. Level of Evidence: N/A

Spontaneous Facet Joint Osteoarthritis in NFAT1-Mutant Mice

“…Surgically or chemically induced OA animal models requires invasive local manipulations to produce mostly unilateral OA with acute joint inflammation and rapid disease progression. [15][16][17][18][19] In contrast, spontaneous OA animal models develop without invasive local manipulations but may be mediated by systemic genetic predisposition, which usually occur bilaterally with slow progression, resembling primary or idiopathic OA in humans. [29][30][31] The STR/ort mouse with a piebald mutation is a widely used spontaneous mouse OA model developed by carcinogen treatment; additional spontaneous animal OA models were developed using transgenic technologies.…”

“…7,[11][12][13][14] To understand the pathogenesis of FJOA, several rodent models of FJOA were generated by invasive local manipulations such as intra-articular injection of chemical agents including collagenase, plasminogen activator, and monosodium iodoacetate (MIA) [15][16][17] , or through direct traumatic/mechanical injury to the articular surface or joint structure. [18][19][20] Those chemically or mechanically induced animal models have improved our understanding of morphological and metabolic changes in post-traumatic FJOA. However, the etiology and unilateral characteristics of those invasive FJOA animal models with acute inflammation and rapid disease progression are distinct from that of spontaneous FJOA in humans that usually occurs bilaterally with slow disease progression.…”

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

“…Lumbar spinal facet joint arthritis is considered clinically important sources of low back pain [ 19 ]. Animal models of LFJ OA are used extensively in research of its pathogenesis [ 20 , 21 ]. Human beings are bipedal, and the loading acts on the lumbar spine were often assumed to be different from those in quadrupeds [ 22 ].…”

“…Recently, research focusing on LFJ OA has been conducted using various animal models [ 2 , 21 ]. In our current study, we reproduced a natural LFJ OA in a novel bipedal standing mouse model that was consistent with a previously described model [ 17 ].…”

Spontaneous Facet Joint Osteoarthritis in NFAT1-Mutant Mice

“…T H E J O U R N A L O F B O N E & JOINT SURGERY d J B J S . O R G VOLUME 104-A d NUMBER 10 d M AY18, 2022 …”