Cite this article: Bone Joint Res 2023;12(3):199–201.

Aims. Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism. Methods. Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1β; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67. phox. was involved in suramin-enhanced chondrocyte phenotype maintenance. Results. Suramin enhanced the COL2A1 and ACAN expression and lowered COL1A1 synthesis. Also, in 3D pellet culture GAG and COL2A1 production was significantly higher in pellets consisting of chondrocytes expanded with suramin compared to controls. Surprisingly, suramin also increased ROS generation, which is largely caused by enhanced NOX (p67. phox. ) activity and membrane translocation. Overexpression of p67. phox. but not p67. phox. AD (deleting amino acid (a.a) 199 to 212) mutant, which does not support ROS production in chondrocytes, significantly enhanced chondrocyte phenotype maintenance, SOX9 expression, and AKT (S473) phosphorylation. Knockdown of p67. phox. with its specific short hairpin (sh) RNA (shRNA) abolished the suramin-induced effects. Moreover, when these cells were treated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor LY294002 or shRNA of AKT1, p67. phox. -induced COL2A1 and ACAN expression was significantly inhibited. Conclusion. Suramin could redifferentiate dedifferentiated chondrocytes dependent on p67. phox. activation, which is mediated by the PI3K/AKT/SOX9 signalling pathway. Cite this article: Bone Joint Res 2022;11(10):723–738

Aims. Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Methods. Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining. Results. Suramin inhibited IL-1β-induced apoptosis, downregulated matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5, and upregulated collagen 2A (Col2a1) and aggrecan in IL-1β-treated NP cells. IL-1β-induced inflammation, assessed by IL-1β, IL-8, and tumour necrosis factor α (TNF-α) upregulation, was alleviated by suramin treatment. Suramin suppressed IL-1β-mediated proteoglycan depletion and the induction of MMP-3, ADAMTS-4, and pro-inflammatory gene expression in ex vivo experiments. Conclusion. Suramin administration represents a novel and effectively therapeutic approach, which could potentially alleviate IDD by reducing extracellular matrix (ECM) deposition and inhibiting apoptosis and inflammatory responses in the NP cells. Cite this article: Bone Joint Res 2021;10(8):498–513

Even when the bone fusion has been successful, the pain may continue to ruin the life of the patient. Two mechanisms have been identified as origin of the pain, one extra and one intradural. The compressive extradural lesions are caused mainly by the action of progressive stenoses or by the disruption of the pedicular wall by badly placed screws. As for defective screw’s trajectory, the most dangerous points are mainly the pedicle’s medial or inferior corticals. In the intraforaminal trajectory the dural sleeve of the lumbar root may be mangled too, suffering a mixed mechanicalbiological mismanagement. Even without laceration a burst cortical or the metal contact can be the origin of root irritation or even palsies. These lesions are present in most series in between 1 and 10% of the screws, depending of the surgical experience. The use of navigational devices finds in this technique his principal indication. The CAT usually diagnoses the misplaced screws. The artefacts caused by stainless steel are the reason of banning this metal for spinal devices. When doubt the pain origin can be proved by electromyographical analysis. The electrical stimulus of the screw with a 0.2 millisecond pulse of 5 – 10 mA DC signals a violated pedicle wall. The treatment of these lesions is always the removal of compressive hardware. When a non-union compounds the root compression a TLIF with cage plus posterolateral fusion with posterior instrumentation, allows the liberation of the root without entering the compromised canal. The compression of the dural sac by recurrent stenosis was frequent in posterior fusions. The lamina thickens by the transmission of charges through this bony continuum. Nowadays it can be yet seen with lamina decortication and bone grafts stocked between the rods and the base of the spinous process. The CT myelogram shows the lesion. The extraction of the hardware and resection of the redundant bone inside the canal, can resolve the compression. The most fearful lesions are the peridural and the intradural fibrosis caused by the operative mishandling of the dural sac or by septic epidural episodes. The neurologic lesions are often irreversible. The treatment is the most difficult and the outcomes the gloomiest of the spinal surgery. The best treatment is the prevention by delicate handling of the dural sac. Suture with titanium micro-clips must be done in all the dural wounds. Disc resection adjoining articular fusion in the treatment of stenotic canals must be avoided, to prevent a cicatricial circle. Abstention of foreign bodies inside the canal, use of bipolar cautery and soluble haemostatic substances to stop the intra-canalar bleeding, are the means of preventing the peridural fibrosis. Corticoids locally or covering the dura with a thin layer of anti-adhesive gel is a good prevention of adherences. The wounds of the dura can produce too a leakage of CSF leading to a compressive myelomeningocele if intracanalar. Wear titanium particles can be found in defective constructs. The motion between rod and screws can produce them. If the particles enter the canal they can produce both compression and fibrosis. In the case intradural adherences blocking the roots in bundles, little can be done. Once secured the immobilisation of the level by a good extracanalar bone-fusion, the use of electrical interference electrodes in contact with the affected roots is the only solution. Some aid can be expected with the use of antiproliferative cytokines as interferon gamma or reverse-transcriptase inhibitors as Suramin, administered after a surgical cleaning of the fibrosis. With all the inconveniences of these treatments yet they allow a modicum of hope