Inhibitory Effects of Human Primary Intervertebral Disc Cells on Human Primary Osteoblasts in a Co-Culture System.

Rahel D May,Sandro Kohl,Christoph E Albers,Benjamin Gantenbein,Daniela A Frauchiger,Lorin M Benneker

doi:10.3390/ijms19041195

Rahel D May, Sandro Kohl + Show 4 more

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https://doi.org/10.3390/ijms19041195

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Abstract

Spinal fusion is a common surgical procedure to address a range of spinal pathologies, like damaged or degenerated discs. After the removal of the intervertebral disc (IVD), a structural spacer is positioned followed by internal fixation, and fusion of the degenerated segment by natural bone growth. Due to their osteoinductive properties, bone morphogenetic proteins (BMP) are applied to promote spinal fusion. Although spinal fusion is successful in most patients, the rates of non-unions after lumbar spine fusion range from 5% to 35%. Clinical observations and recent studies indicate, that the incomplete removal of disc tissue might lead to failure of spinal fusion. Yet, it is still unknown if a secretion of BMP antagonists in intervertebral disc (IVD) cells could be the reason of inhibition in bone formation. In this study, we co-cultured human primary osteoblasts (OB) and IVD cells i.e., nucleus pulposus (NPC), annulus fibrosus (AFC) and cartilaginous endplate cells (CEPC), to test the possible inhibitory effect from IVD cells on OB. Although we could see a trend in lower matrix mineralization in OB co-cultured with IVD cells, results of alkaline phosphatase (ALP) activity and gene expression of major bone genes were inconclusive. However, in NPC, AFC and CEPC beads, an up-regulation of several BMP antagonist genes could be detected. Despite being able to show several indicators for an inhibition of osteoinductive effects due to IVD cells, the reasons for pseudarthrosis after spinal fusion remain unclear.

Highlights

Chronic low back pain (LBP) is a global disease that has evolved into a socio-economic burden [1,2,3]
Due to the advancement of minimal invasive surgeries, such as laparoscopic anterior spinal fusion, it has become more challenging to remove all the disc tissue sufficiently. This is of high importance as clinical observations indicate that partial removal of the disc during discectomy might cause failure in bone formation. This is in accordance with recent findings by Chan et al, which showed that mesenchymal stromal cells (MSC) are hindered to undergo osteogenesis when co-cultured with intervertebral disc (IVD) cells but are stimulated to undergo bone formation with osteogenic medium [9]
This study aimed to investigate the osteoinductive effects on OB when co-cultured with the different types of IVD cells, i.e., nucleus pulposus cells (NPC), AFC and cartilaginous endplate cells (CEPC)

Summary

Introduction

Chronic low back pain (LBP) is a global disease that has evolved into a socio-economic burden [1,2,3]. Due to the advancement of minimal invasive surgeries, such as laparoscopic anterior spinal fusion, it has become more challenging to remove all the disc tissue sufficiently. This is of high importance as clinical observations indicate that partial removal of the disc during discectomy might cause failure in bone formation. This is in accordance with recent findings by Chan et al, which showed that mesenchymal stromal cells (MSC) are hindered to undergo osteogenesis when co-cultured with IVD cells but are stimulated to undergo bone formation with osteogenic medium [9]. Li et al indicated, in an in vivo pig model, an unsuccessful spinal fusion due to presence of nucleus pulposus cells (NPC) [10]

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