Novel Collagen Biomarkers of Intervertebral Disc Degeneration And Candidate Molecules For Regeneration -Inferences from Comparative Proteomic Analysis Of Fetal, Healthy Adult And Diseased Discs — The International Society for the Study of the Lumbar Spine

Novel Collagen Biomarkers of Intervertebral Disc Degeneration And Candidate Molecules For Regeneration -Inferences from Comparative Proteomic Analysis Of Fetal, Healthy Adult And Diseased Discs (#1028)

S Dilip Chand Raja 1 , Shanmuganathan Rajasekaran 1 , Sri Vijay Anand K S 1 , Sharon Miracle Nayagam 2 , Sunmathi R 2 , Chitraa Tangavel 2 , Ajoy Shetty 1 , Rishi Kanna 1
  1. Ganga hospital, Coimbatore, TAMIL NADU, India
  2. Department of Proteomics, Ganga Research Centre, Coimbatore, Tamil Nadu, India

Introduction: Alterations in the collagen (COL) composition have been correlated to degenerative disc disease (DDD). Though 28 different types of COLs are present in humans, most of the literature is focused only on COL-1 and COL-2. There are no detailed studies evaluating the collagen types and their significance in IVD. The current study aimed to analyze the entire COL composition of human intervertebral disc (IVD) across fetal (developmental-FD), normal (healthy-ND), scoliotic (early degeneration-SD), herniated (degenerate-DH), and degenerated (DD) disc phenotypes using high-end proteomic-technology.

Methods: Forty Nucleus pulposus (NP) tissues segregated from from five different disc phenotypes (eight each) under sterile conditions were snap-frozen in liquid nitrogen ((LN2) -196⁰C) immediately before subjecting to proteomic and bioinformatic analysis.

Results: Tandem mass spectrometric analysis revealed a total of 1050 proteins in fetal discs (FD); 1809 in ND; 1487 in SD; 1859 in DH and 1538 in the DD group. Out of 28 major collagens reported in human body, this study identified 24 different Collagens with 34 subtypes in NP. Fibril forming collagens (COL-1,2 and 11A1) and Fibril associated collagens with interrupted triple helices (COL-9A1,12A1 and 14A1) were abundantly expressed in fetal discs representing their role in development of NP. More importantly Multiplexin (COL-15), a hybrid proteoglycan/collagen molecule was found only in fetal discs. Downregulation of COL2A1 and upregulation of COL-10A1 was associated with degeneration.

Conclusion: COL10 was identified as a novel biomarker for disc degeneration. Apart from COL-1 and 2, other important COLs (6,9,11,12,14 and 15) with anabolic potential, abundantly expressed in fetal phenotype could be explored for tissue engineering and regenerative therapies for DDD.

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