Facet joint degeneration in adolescent idiopathic scoliosis

Abstract

Adolescent idiopathic scoliosis (AIS) is a poorly understood deformity of the thoracolumbar spine which affects the intervertebral discs (IVDs) and the articular facet joints. The knowledge concerning facet joints in this context is very limited, although facet joint degeneration is a known contributor of back pain. In this study, a comprehensive investigation was performed to characterize the facet joint chondrocytes and extracellular matrix within the scoliotic spine. Surgically removed articular facet joint tissues were collected from patients undergoing spinal corrective surgery for AIS deformities, while non‐scoliotic articular facet joint tissues were obtained from cadaveric organ donors. Alterations in cartilage tissue structure were evaluated histologically with safranin‐O fast green and a modified OARSI grading scale. Pro‐inflammatory cytokines, matrix‐degrading proteases, and fragmented matrix molecules associated with cartilage degradation were analyzed by immunohistochemistry and western blotting. Safranin‐O fast green staining revealed that young scoliotic facet joints show clear signs of degeneration with substantial proteoglycan loss, similar to osteoarthritis (OA). The proteoglycan levels were significantly lower than in healthy asymptomatic non‐scoliotic control individuals. In comparison to controls, scoliotic articular facets showed increased cell density, increased expression of the proliferation marker Ki‐67, and higher expression of MMP‐3, MMP‐13, and IL‐1β. Expression and fragmentation of the small leucine‐rich proteins (SLRPs) chondroadherin, decorin, biglycan, lumican, and fibromodulin were analyzed with western blot. Chondroadherin and decorin were fragmented in cartilage from patients with a curve greater than 70°, whereas biglycan and fibromodulin did not show curve‐related fragmentation. AIS facet joint cartilage shows hallmarks of OA including proteoglycan loss, overexpression of pro‐inflammatory mediators, increased synthesis of matrix‐degrading proteases and fragmentation of SLRPs. As with patients with age‐related OA, the premature joint degeneration seen in scoliotic patients is likely to contribute to the pain perceived in some individuals.

Toll‐like receptor involvement in adolescent scoliotic facet joint degeneration

“…The increase in baseline gene expression of proteases MMP3 and MMP13 match extensive previous research showing a robust increase of these proteases in OA cartilage. Furthermore, it corroborates with immunohistochemistry findings in our previous study on scoliotic facet joint degeneration 4 . Gene expression analysis of TLRs revealed that chondrocytes from degenerating scoliotic cartilage had an elevated baseline expression of TLRs compared with the non‐degenerate non‐scoliotic cells.…”

“…Similarly, we have recently reported facet joint osteoarthritis (OA) in AIS patients, although, how the altered biomechanics affect the facet joints is still unclear. Histologically, we found that scoliotic and non‐scoliotic facet joint OA share many characteristics such as fibrillation of the cartilage surface, erosion, fissuring, osteophyte formation, increased cell density and elevated expression of pro‐catabolic and pro‐inflammatory factors which suggests that they are closely related 4,9,10 …”

“…Histologically, we found that scoliotic and non-scoliotic facet joint OA share many characteristics such as fibrillation of the cartilage surface, erosion, fissuring, osteophyte formation, increased cell density and elevated expression of pro-catabolic and pro-inflammatory factors which suggests that they are closely related. 4,9,10 The underlying pathology of facet joint OA is a catabolic and inflammatory environment that leads to degradation, loss of function and potentially pain. Pro-inflammatory cytokines are secreted by chondrocytes and synovial fibroblasts and cause catabolism by triggering the production of proteases degrading the extracellular matrix (ECM).…”

“…Many studies have confirmed the detrimental effects of non‐physiological loading on both facet joints and IVDs, as well as segmental degeneration following injurious loading. One such example is the presence of IVD and facet joint degeneration in adolescent idiopathic scoliosis (AIS) 4‐6 . AIS is the most prevalent orthopaedic condition (up to 4%) in young individuals aged from 10 to 16 worldwide that involves a progressive curvature of the spine 7 .…”

From Translation to Protein Degradation as Mechanisms for Regulating Biological Functions: A Review on the SLRP Family in Skeletal Tissues

“…The fragmentation of chondroadherin is also characteristic of the disease, the cleavage site-specific for disc degeneration is represented in Table 2, making the chondroadherin fragment an efficient biomarker [127,137]. In addition, other SLRPs present enhanced fragmentation patterns in pathological human and canine intervertebral discs [138][139][140].…”