Abstract
BackgroundIntervertebral disc (IVD) herniation is characterized by annulus fibrosus failure (AF) in containing the nucleus pulposus (NP). IVD herniation involves cellular and extracellular matrix (ECM) alterations that have been associated with tissue fibrosis, although still poorly investigated.MethodsHere, fibrotic alterations in human AF were evaluated, by characterizing the herniated ECM. Human AF samples (herniated lumbar IVD (n = 39, age 24–83) and scoliosis controls (n = 6, age 15–21)) were processed for transmission electron microscopy and histological/immunohistochemical analysis of fibrotic markers. Correlations between the fibrotic markers in AF ECM and the degree of NP containment (protused, contained and uncontained) and patients’ age were conducted.ResultsOur results demonstrate that with herniation progression, i.e. loss of NP containment, human AF presents less stained area of sulphated glycosaminoglycans and collagen I, being collagen I fibres thinner and disorganized. On the other hand, fibronectin stained area and percentage of α-smooth muscle actin+ cells increase in human AF, while matrix metalloproteinase-12 (MMP12) production and percentage of macrophages (CD68+ cells) remain constant. These structural and biochemical fibrotic alterations observed in human AF with herniation progression occur independently of the age.ConclusionsThe characterization of human AF here conducted evidence the presence of fibrosis in degenerated IVD, while highlighting the importance of considering the herniation progression stage, despite the patients’ age, for a better understanding of the mechanisms behind AF failure and IVD herniation.
Highlights
Intervertebral disc (IVD) herniation is characterized by annulus fibrosus failure (AF) in containing the nucleus pulposus (NP)
Results human AF (hAF) matrix structural analysis with herniation progression The hAF was obtained from herniated IVD biopsies collected from patients undergoing microdiscectomy
A macroscopic dissection of IVD samples to isolate the AF tissue was first performed (Fig. 1A). hAF from herniated samples was separated into three categories, according to the information provided by the neurosurgeon: protused, contained and uncontained (Fig. 1B)
Summary
Intervertebral disc (IVD) herniation is characterized by annulus fibrosus failure (AF) in containing the nucleus pulposus (NP). IVD herniation involves cellular and extracellular matrix (ECM) alterations that have been asso‐ ciated with tissue fibrosis, still poorly investigated. ECM alterations are characterized by an increase in collagen I (Col I) content and fibronectin (FN) deposition, accompanied by matrix disorganization, leading to scar tissue formation and eventually resulting in organ dysfunction [10, 14]. Macrophages regulate fibrosis since they are high producers of transglutaminases and matrix metalloproteinases (MMPs) [21, 26] Their presence in herniated IVDs has been extensively reported [27, 28], as well as MMPs, but only MMP12 has been suggested as fibrotic marker for IVD degeneration [12, 29]
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