The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, UCLA School of Dentistry, Los Angeles, CA, USA.
Biomaterials. 2013 Aug;34(26):6147-56. doi: 10.1016/j.biomaterials.2013.04.064. Epub 2013 May 24.
Bone regeneration often requires cues from osteogenesis-inducing factors for successful outcome. N-acetyl cysteine (NAC), an anti-oxidant small molecule, possibly modulates osteoblastic differentiation. This study investigated the potential of NAC as an osteogenesis-enhancing molecule in vitro and in vivo. Various concentrations of NAC (0, 2.5, 5.0, and 10 mM) were added to rat bone marrow stromal cell or osteoblastic cell culture in media with or without dexamethasone. The results showed marked enhancement of alkaline phosphatase activity and mineralized matrix formation together with consistent upregulation of bone-related gene markers such as collagen I, osteopontin, and osteocalcin in the osteoblastic culture with addition of 2.5 or 5.0 mM NAC regardless of the presence of dexamethasone. Micro-CT-based analysis and histological observation revealed that addition of NAC to a collagenous sponge implanted in a critical size cortical bone defect (3.0 mm × 5.0 mm) in rat femur yielded acceleration and completion of defect closure, with thick, compact, and contiguous bone after 6 weeks of healing. In contrast, with sponge alone, only sparse and incomplete bone regeneration was observed during the matching healing period. These results indicate that NAC can function as an osteogenesis-enhancing molecule to accelerate bone regeneration by activating differentiation of osteogenic lineages.
骨再生通常需要成骨诱导因子的信号来获得成功。N-乙酰半胱氨酸 (NAC) 是一种抗氧化小分子，可能调节成骨细胞分化。本研究旨在体外和体内研究 NAC 作为一种增强成骨作用的分子的潜力。在含有或不含有地塞米松的培养基中，将不同浓度的 NAC（0、2.5、5.0 和 10 mM）添加到大鼠骨髓基质细胞或成骨细胞培养物中。结果表明，在添加 2.5 或 5.0 mM NAC 的成骨细胞培养物中，碱性磷酸酶活性和矿化基质形成明显增强，同时伴随着骨相关基因标志物如 I 型胶原、骨桥蛋白和骨钙素的一致上调，无论是否存在地塞米松。基于微 CT 的分析和组织学观察表明，在大鼠股骨 3.0mm×5.0mm 皮质骨缺损（critical size cortical bone defect）中植入胶原海绵的同时添加 NAC，可加速和完成缺损闭合，在 6 周的愈合期后，形成厚而致密且连续的骨。相比之下，单独使用海绵，仅在匹配的愈合期观察到稀疏和不完整的骨再生。这些结果表明，NAC 可作为一种增强成骨作用的分子，通过激活成骨谱系的分化来加速骨再生。
