Spatiotemporal Expression of 3-B-3(−) and 7-D-4 Chondroitin Sulfation, Tissue Remodeling, and Attempted Repair in an Ovine Model of Intervertebral Disc Degeneration. (April 2020)

• Record Type: Journal Article
• Authors: Farrugia, Brooke; Smith, Susan M.; Shu, Cindy C.; Melrose, James
• Other Names: Roberts Sally guest-editor.; Kandel Rita guest-editor.
• Is Part Of: Cartilage. Volume 11:Number 2(2020)
• Page Start: 234
• Page End: 250
• Publication Date: 2020-04
• Subjects: chondroitin sulfate motifs -- tissue remodeling -- tissue regeneration -- 3-B-3(−) -- 7-D-4 -- annular repair; Cartilage -- Periodicals; 616.7
• DOI: 10.1177/1947603519876354
• Languages: English
• ISSNs: 1947-6035

Abstract

Objective: Examination of intervertebral disc (IVD) regeneration in an ovine annular lesion model. Hypothesis: Sulfation motifs are important functional determinants in glycosaminoglycans (GAGs). Previous studies have correlated 3-B-3(−) and 7-D-4 chondroitin sulfate (CS) motifs in tissues undergoing morphogenetic transition in development. We hypothesize that these motifs may also be expressed in degenerate IVDs and may represent a reparative response. Design: Induction of disc degeneration by 5 mm or 6 × 20 mm lesions in the annulus fibrosus (AF) over 6 or 3 to 6 months postoperation (PO). Tissue sections were stained with toluidine blue–fast green, 3-B-3(−) and 7-D-4 CS-sulfation motifs were immunolocalized in 3-month PO 6 × 20 mm lesion IVDs. Sulfated glycosaminoglycan (GAG), 3-B-3(−), and 7-D-4 epitopes were quantitated by ELISIA (enzyme-linked immunosorbent inhibition assay) in extracts of AF (lesion site and contralateral half) and nucleus pulposus (NP) 0, 3, and 6 months PO. Results: Collagenous overgrowth of lesions occurred in the outer AF. Chondroid metaplasia in ~20% of the 6 × 20 mm affected discs resulted in integration of an outgrowth of NP tissue with the inner AF lamellae preventing propagation of the lesion. 3-B-3(−) and 7-D-4 CS sulfation motifs were immunolocalized in this chondroid tissue. ELISIA quantified CS sulfation motifs demonstrating an increase 3 to 6 months PO in the AF lesion and a reduction in sulfated GAG not evident in the contralateral AF. Conclusions: (1) Outer annular lesions underwent spontaneous repair. (2) Chondroid metaplasia of the inner 6 × 20 mm defect prevented its propagation suggesting an apparent reparative response.