背景:骨形态发生蛋白(BMP)具有有效的骨诱导性,已在临床上用于具有挑战性的肌肉骨骼疾病。然而,在临床环境中使用的BMP的超生理剂量会引起各种副作用,阻止广泛使用,因此需要减少BMP剂量。
目标:为了解决这个问题,我们合成了7C,视黄酸受体γ拮抗剂纳米粒(NP),并使用大鼠脊柱融合模型研究了其在基于BMP的骨再生治疗中的潜在应用。
方法:实验动物研究。
方法:53只8周龄雄性Sprague-Dawley大鼠行脊柱后外侧融合术,分为以下5个治疗组:(1)无重组人(rh)BMP-2和空白-NP(对照),(2)无rhBMP-2和1μg7C-NP(7C组),(3)低剂量rhBMP-2(0.5μg)和1μg空白NP(L-BMP组),(4)低剂量rhBMP-2(0.5μg)和1μg7C-NP(L-BMP7C组),和(5)高剂量rhBMP-2(5.0μg)和1μg空白-NP(H-BMP组)。手术后2周和6周进行显微计算机断层扫描和组织学分析。
结果:对照组和7C组的脊柱融合率均为0%,还有L-BMP,L-BMP+7C,H-BMP组为55.6%,94.4%,100%,分别。在BMP诱导的软骨内骨形成过程中,L-BMP7C组可显着促进软骨组织的形成,从而使脊柱融合率和骨形成明显优于L-BMP组。尽管L-BMP+7C组的脊柱融合速度较慢,与H-BMP组相比,L-BMP+7C组形成的脊柱融合块具有更好的骨质量。
结论:在大鼠腰椎后外侧融合模型中联合使用7C-NP和rhBMP-2可提高脊柱融合率和新骨体积,而不会降低新形成的骨质量。
结论:7C-NP可增强BMP-2诱导的骨再生,并具有低剂量BMP-2有效骨再生的潜力,可减少BMP-2的剂量依赖性副作用。
BACKGROUND: Bone morphogenetic proteins (BMPs) have potent osteoinductivity and have been applied clinically for challenging musculoskeletal conditions. However, the supraphysiological doses of BMPs used in clinical settings cause various side effects that prevent widespread use, and therefore the BMP dosage needs to be reduced.
OBJECTIVE: To address this problem, we synthesized 7C, a retinoic acid receptor γ antagonist-loaded nanoparticle (NP), and investigated its potential application in BMP-based bone regeneration therapy using a rat spinal fusion model.
METHODS: An experimental animal study.
METHODS: Fifty-three male 8-week-old Sprague-Dawley rats underwent posterolateral spinal fusion and were divided into the following five treatment groups: (1) no recombinant human (rh)BMP-2 and blank-NP (Control), (2) no rhBMP-2 and 1 μg 7C-NP (7C group), (3) low-dose rhBMP-2 (0.5 μg) and 1 μg blank-NP (L-BMP group), (4) low-dose rhBMP-2 (0.5 μg) and 1 μg 7C-NP (L-BMP + 7C group), and (5) high-dose rhBMP-2 (5.0 μg) and 1 μg blank-NP (H-BMP group). Micro-computed tomography and histologic analysis were performed 2 and 6 weeks after the surgery.
RESULTS: The spinal fusion rates of the Control and 7C groups were both 0%, and those of the L-BMP, L-BMP + 7C, and H-BMP groups were 55.6%, 94.4%, and 100%, respectively. The L-BMP + 7C group markedly promoted cartilaginous tissue formation during BMP-induced endochondral bone formation that resulted in a significantly better spinal fusion rate and bone formation than in the L-BMP group. Although spinal fusion was slower in the L-BMP + 7C group, the L-BMP + 7C group formed a spinal fusion mass with better bone quality than the spinal fusion mass in the H-BMP group.
CONCLUSIONS: The combined use of 7C-NP with rhBMP-2 in a rat posterolateral lumbar fusion model increased spinal fusion rate and new bone volume without deteriorating the quality of newly formed bone.
CONCLUSIONS: 7C-NP potentiates BMP-2-induced bone regeneration and has the potential for efficient bone regeneration with low-dose BMP-2, which can reduce the dose-dependent side effects of BMP-2 in clinical settings.