Baugé Catherine, Leclercq Sylvain, Conrozier Thierry, Boumediene Karim
Normandie Univ, Caen, France.
EA4652 Equipe BioConnecT, UFR de médecine, Université de Caen, CS14032 Caen cedex 5, Caen, France.
BMC Complement Altern Med. 2015 Jul 9;15:217. doi: 10.1186/s12906-015-0748-7.
Tendinopathies are tendon conditions associated with degeneration and disorganization of the matrix collagen fibers, tendon cells apoptosis and inflammation through up-regulation of proinflammatory cytokines, matrix metalloproteinase (MMP) expression, and prostaglandin E2 (PGE2) production. Currently, the pharmacological treatment is mainly based on non-steroidal anti-inflammatory drugs (NSAIDs) use and corticosteroid injections, which both can lead to numerous side effects for patients. TOL19-001 is a diet supplementary composed mostly of spirulina and glucosamine sulfate whose antioxidant properties could be helpful to treat tendinopathies while avoiding taking NSAIDs. In this study we developed an in vitro model of tendinopathy in order to evaluate the therapeutic potential of TOL19-001.
Tendon cells were cultured on monolayer and treated with interleukin-1β (IL-1β) or ciprofloxacin (CIP), and then, MMPs, PGE2 and collagen expression was evaluated by RT-PCR or Elisa. In addition, a cotreatment with increased doses of TOL19-001 was done. Toxicity of TOL19-001 was evaluated using a metabolic activity assay.
This study demonstrates that IL-1β mimics some aspects of tendinopathies with PGE2 induction, MMP expression (mostly MMP1 and MMP3), and increases of type III/I collagen ratio. CIP, meanwhile, leads to an increase of MMP2 and p65 mRNA, whereas it reduces TIMP1 expression. Scleraxis expression was also increased by CIP whereas it was decreased by IL-1β treatment. Besides, TOL19-001 cotreatment suppresses tendon cell inflammation in vitro, marked by the downregulation of PGE2, MMPs and type III collagen in IL-1β stimulated-cells. TOL19-001 also represses CIP induced-changes.
These findings indicate that TOL19-001 exerts anti-inflammatory effects on tendon cells, which might explain why TOL19-001 diet may improve tendon function in patients with tendon injury. Future research is required to determine TOL19-001 effect on injured or overused tendons in vivo.
肌腱病是与基质胶原纤维变性和紊乱、肌腱细胞凋亡以及通过促炎细胞因子上调、基质金属蛋白酶（MMP）表达和前列腺素E2（PGE2）产生相关的炎症有关的肌腱病症。目前，药物治疗主要基于使用非甾体抗炎药（NSAIDs）和皮质类固醇注射，这两者都会给患者带来许多副作用。TOL19-001是一种主要由螺旋藻和硫酸葡萄糖胺组成的饮食补充剂，其抗氧化特性可能有助于治疗肌腱病，同时避免服用NSAIDs。在本研究中，我们建立了一种肌腱病的体外模型，以评估TOL19-001的治疗潜力。
将肌腱细胞培养成单层，并用白细胞介素-1β（IL-1β）或环丙沙星（CIP）处理，然后通过RT-PCR或酶联免疫吸附测定法评估MMPs、PGE2和胶原蛋白的表达。此外，进行了增加剂量的TOL19-001的联合治疗。使用代谢活性测定法评估TOL19-001的毒性。
本研究表明，IL-1β通过诱导PGE2、MMP表达（主要是MMP1和MMP3）以及增加III型/I型胶原蛋白比例，模拟了肌腱病的某些方面。同时，CIP导致MMP2和p65 mRNA增加，而降低TIMP1表达。CIP还增加了硬骨素表达，而IL-1β处理则降低了硬骨素表达。此外，TOL19-001联合治疗在体外抑制肌腱细胞炎症，其特征是IL-1β刺激的细胞中PGE2、MMPs和III型胶原蛋白下调。TOL19-001还抑制CIP诱导的变化。
这些发现表明，TOL19-001对肌腱细胞具有抗炎作用，这可能解释了为什么TOL19-001饮食可以改善肌腱损伤患者的肌腱功能。未来需要进行研究以确定TOL19-001对体内受伤或过度使用的肌腱的影响。
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