未经证实:椎间盘(IVD)变性被认为是慢性下腰痛(LBP)的主要原因。已提出将生长因子的椎间盘内递送作为IVD修复和再生的有希望的策略。以前,在人髓核(NP)细胞中,BMP-4在促进细胞外基质(ECM)产生方面比其他BMP和TGF-β更有效。表明它适用于椎间盘再生。
UNASSIGNED:在颗粒培养模型中,在绵羊NP和纤维环(AF)细胞中评估BMP-4对ECM沉积和细胞增殖的影响。Further,采用核切诱导的绵羊腰椎IVD退变模型,评价椎间盘内注射BMP-4对IVD再生的安全性和效果.结果通过磁共振成像评估,显微计算机断层扫描,组织学和生化测量。
未经评估:体外,BMP-4显著增加蛋白多糖的产生和II型胶原的沉积以及NP和AF细胞的增殖。NP细胞中I型胶原沉积未受影响,而在AF细胞中,它在低BMP-4浓度下很高,并随着BMP-4浓度的增加而降低。椎间盘内注射BMP-4诱导体内椎间盘外新骨形成和Schmorl结节样变化。在NP和AF中均未观察到再生。
UNASSIGNED:我们的研究表明,尽管BMP-4在体外显示出有希望的再生作用,在大型IVD变性动物模型中未观察到类似效果.
UNASSIGNED:使用BMP-4对体外和体内IVD再生的矛盾结果表明,直接注射BMP-4治疗椎间盘退变相关的人类慢性下腰痛不应该进行。此外,我们的结果也可能揭示人类患者病理性终板改变背后的机制,作为可能的治疗靶点.
UNASSIGNED: Intervertebral disc (IVD) degeneration is suggested as a major cause of chronic low back pain (LBP). Intradiscal delivery of growth factors has been proposed as a promising strategy for IVD repair and regeneration. Previously, BMP-4 was shown to be more potent in promoting extracellular matrix (ECM) production than other BMPs and TGF-β in human nucleus pulposus (NP) cells, suggesting its applicability for disc regeneration.
UNASSIGNED: The effects of BMP-4 on ECM deposition and cell proliferation were assessed in sheep NP and annulus fibrosus (AF) cells in a pellet culture model. Further, a nuclectomy induced sheep lumbar IVD degeneration model was used to evaluate the safety and effects of intradiscal BMP-4 injection on IVD regeneration. Outcomes were assessed by magnetic resonance imaging, micro-computed tomography, histological and biochemical measurements.
UNASSIGNED: In vitro, BMP-4 significantly increased the production of proteoglycan and deposition of collagen type II and proliferation of NP and AF cells. Collagen type I deposition was not affected in NP cells, while in AF cells it was high at low BMP-4 concentrations, and decreased with increasing concentration of BMP-4. Intradiscal injection of BMP-4 induced extradiscal new bone formation and Schmorl\'s node-like changes in vivo. No regeneration in the NP nor AF was observed.
UNASSIGNED: Our study demonstrated that although BMP-4 showed promising regenerative effects in vitro, similar effects were not observed in a large IVD degeneration animal model.
UNASSIGNED: The contradictory results of using BMP-4 on IVD regeneration between in vitro and in vivo demonstrate that direct BMP-4 injection for disc degeneration-associated human chronic low back pain should not be undertaken. In addition, our results may also shed light on the mechanisms behind pathological endplate changes in human patients as a possible target for therapy.