Aims

This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

Aims

Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

Aims

Inflammatory response plays a pivotal role in the pathophysiological process of intervertebral disc degeneration (IDD). A20 (also known as tumour necrosis factor alpha-induced protein 3 (TNFAIP3)) is a ubiquitin-editing enzyme that restricts nuclear factor-kappa B (NF-κB) signalling. A20 prevents the occurrence of multiple inflammatory diseases. However, the role of A20 in the initiation of IDD has not been elucidated. The aim of the study was to investigate the effect of A20 in senescence of TNF alpha (TNF-α)-induced nucleus pulposus cells (NPCs).

Introduction. Spinal deformations are a deviation of the natural arrangement of forces during growth. Environmental factors play a part in these deviations. The presence of lordosis in the thoracic spine is a causative factor in spinal deformations that needs to be addressed. Most biomechanical models of bracing have a scientific background. Has older knowledge lost its value? In living structures, all processes such as regulation of equilibrium in posture and movement use Newton's law and extended laws of Hooke for conservation of energy, momentum, and angular momentum under control of the central nervous system. Form follows function (phylogenetic and ontogenetic) in the spine as primary engine in movement in animals. The change in function in bipedals is that the coupling mechanism at the thoracolumbar joint now couples a reversed pendulum. Methods. A literature search shows a clear gap in the evolution in science on deformities during 1914–45. In 1792, Van Gesscher postulated two concepts in Observations on Deformations of the Spine (Dutch). First, the optimalisation of the balancing forces in men needs a specific optimum curvature to keep the weight of the head and shoulders above the hips. The second concept was the role of sitting in relation to changes around the discs at the thoracolumbar spine. Girls who read or knitted while sitting developed scoliosis more easily than did others. His extending (by lordosis) corrective corset was used for more than 150 years before plaster became popular. Andry described guidance and correction of growing spines with use of the moulding capability of muscular forces, with exercises and extending corsets (for so-called weak girls). Extension and avoidance of incorrect posture during sitting became a mainstay in orthopaedics (and schools). In 1907, Wullstein described experiments in young dogs to show how forced fiexion produces all characteristics of kyphotic deformities. In 1912, Murk Jansen did a critical review of all available knowledge and his own research in The Physiologic Scoliosis and its causes. Post mortem studies showed anatomical asymmetry in the left and right crura of the diaphragm, which indicated that asymmetric rotational forces in ventilation could induce predominant lateral curves. In-vivo tests show increased thoracolumbar kyphosis if siblings are put in seated positions too frequently and too soon. The stiffening in kyphosis creates a fulcrum to cantilever the opposing rotational forces to lateral curvatures. In experiments in rabbits, lower intrathoracic pressure was shown in the right pleural cavity. Common alertness of parents and teachers was underwritten. Some of this still survives. In progressed scoliosis, Sayre's method of corrective plastering in suspension and Calot's corrections in prone position under anaesthesia and plaster shelves with lordosis in bed became popular. In the Volkmann Hueter principle, the resilience of the deformable structures in the spine were identified–eg, the discs, the apophyses, and the cartilage in joints have a role in spinal deformity. Cobb drew attention to the clinical aspects of scoliosis. Roth provided a comprehensive explanation of how growth is organised and regulated by the oldest organ of animal life: the central nervous system in vertebrates. Between 1960 and 1985, Roth developed his concepts on neurovertebral and neuro-osseous growth relations and the tension-driven incongruence of growth. Roth provided new biological knowledge about how growth seems to support older clinical observations. In animal experiments, mechanical modelling, and radiological studies in scoliosis he stressed the role that growth has in the formation of the spine. A so-called short cord can indeed cause scoliosis. Recent studies with MRI in idiopathic scoliosis confirm this hypothesis. Personal observations In 2008, a study showed that forceful restoration of thoracolumbar lordosis can correct double major scoliotic curves. A consequent thoracolumbar kyphotic curve was found, and recently reproduced. The thoracolumbar lordotic intervention brace technique showed promising results. It relied on the older techniques, leaving only the fear for lordosis brought by Dickson. In personal observations, the presence of neuromuscular tightness or tension also present in progressive scoliosis as representatives of deforming and protective forces. Conclusions. Previous knowledge depicts spinal growth as result of a combination of neuro-osseous growth regulation in a very complex but understandable loco-motor system, in which external factors cause muscular reaction that obey all mechanical laws. Lifestyle factors seem to greatly affect deformations

The belief that an intervertebral disc must degenerate before it can herniate has clinical and medicolegal significance, but lacks scientific validity. We hypothesised that tissue changes in herniated discs differ from those in discs that degenerate without herniation. Tissues were obtained at surgery from 21 herniated discs and 11 non-herniated discs of similar degeneration as assessed by the Pfirrmann grade. Thin sections were graded histologically, and certain features were quantified using immunofluorescence combined with confocal microscopy and image analysis. Herniated and degenerated tissues were compared separately for each tissue type: nucleus, inner annulus and outer annulus.

Herniated tissues showed significantly greater proteoglycan loss (outer annulus), neovascularisation (annulus), innervation (annulus), cellularity/inflammation (annulus) and expression of matrix-degrading enzymes (inner annulus) than degenerated discs. No significant differences were seen in the nucleus tissue from herniated and degenerated discs. Degenerative changes start in the nucleus, so it seems unlikely that advanced degeneration caused herniation in 21 of these 32 discs. On the contrary, specific changes in the annulus can be interpreted as the consequences of herniation, when disruption allows local swelling, proteoglycan loss, and the ingrowth of blood vessels, nerves and inflammatory cells.

In conclusion, it should not be assumed that degenerative changes always precede disc herniation.

Cite this article: Bone Joint J 2013;95-B:1127–33.

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc.

Cite this article: Bone Joint Res 2013;2:169–78.

This article reviews the current knowledge of the intervertebral disc (IVD) and its association with low back pain (LBP). The normal IVD is a largely avascular and aneural structure with a high water content, its nutrients mainly diffusing through the end plates. IVD degeneration occurs when its cells die or become dysfunctional, notably in an acidic environment. In the process of degeneration, the IVD becomes dehydrated and vascularised, and there is an ingrowth of nerves. Although not universally the case, the altered physiology of the IVD is believed to precede or be associated with many clinical symptoms or conditions including low back and/or lower limb pain, paraesthesia, spinal stenosis and disc herniation.

New treatment options have been developed in recent years. These include biological therapies and novel surgical techniques (such as total disc replacement), although many of these are still in their experimental phase. Central to developing further methods of treatment is the need for effective ways in which to assess patients and measure their outcomes. However, significant difficulties remain and it is therefore an appropriate time to be further investigating the scientific basis of and treatment of LBP.

Discogenic low back pain is a common cause of disability, but its pathogenesis is poorly understood. We collected 19 specimens of lumbar intervertebral discs from 17 patients with discogenic low back pain during posterior lumbar interbody fusion, 12 from physiologically ageing discs and ten from normal control discs. We investigated the histological features and assessed the immunoreactive activity of neurofilament (NF200) and neuropeptides such as substance P (SP) and vasoactive-intestinal peptide (VIP) in the nerve fibres.

The distinct histological characteristic of the painful disc was the formation of a zone of vascularised granulation tissue from the nucleus pulposus to the outer part of the annulus fibrosus along the edges of the fissures. SP-, NF- and VIP-immunoreactive nerve fibres in the painful discs were more extensive than in the control discs. Growth of nerves deep into the annulus fibrosus and nucleus pulposus was observed mainly along the zone of granulation tissue in the painful discs. This suggests that the zone of granulation tissue with extensive innervation along the tears in the posterior part of the painful disc may be responsible for causing the pain of discography and of discogenic low back pain.