Department of Maxillofacial Tissue Regeneration, School of Dentistry and Institute of Oral Biology, Kyung Hee University, Seoul, Republic of Korea.
J Cell Biochem. 2013 May;114(5):1183-93. doi: 10.1002/jcb.24461.
Although previous studies have demonstrated that hydrogen sulfide (H(2)S) stimulated or inhibited osteoclastic differentiation, little is known about the effects of H(2)S on the differentiation of osteoblasts and osteoclasts. To determine the possible bioactivities of H(2)S on bone metabolism, we investigated the in vitro effects of H(2)S on cytotoxicity, osteoblastic, and osteoclastic differentiation as well as the underlying mechanism in lipopolysaccharide (LPS) and nicotine-stimulated human periodontal ligament cells (hPDLCs). The H(2)S donor, NaHS, protected hPDLCs from nicotine and LPS-induced cytotoxicity and recovered nicotine- and LPS-downregulated osteoblastic differentiation, such as alkaline phosphatase (ALP) activity, mRNA expression of osteoblasts, including ALP, osteopontin (OPN), and osteocalcin (OCN), and mineralized nodule formation. Concomitantly, NaHS inhibited the differentiation of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in mouse bone marrow cells and blocked nicotine- and LPS-induced osteoclastogenesis regulatory molecules, such as RANKL, OPG, M-CSF, MMP-9, TRAP, and cathepsin K mRNA. NaHS blocked nicotine and LPS-induced activation of p38, ERK, MKP-1, PI3K, PKC, and PKC isoenzymes, and NF-κB. The effects of H(2)S on nicotine- and LPS-induced osteoblastic and osteoclastic differentiation were remarkably reversed by MKP-1 enzyme inhibitor (vanadate) and expression inhibitor (triptolide). Taken together, we report for the first time that H(2)S inhibited cytotoxicity and osteoclastic differentiation and recovered osteoblastic differentiation in a nicotine- and periodontopathogen-stimulated hPDLCs model, which has potential therapeutic value for treatment of periodontal and inflammatory bone diseases.
虽然先前的研究表明硫化氢（H2S）可刺激或抑制破骨细胞分化，但对于 H2S 对成骨细胞和破骨细胞分化的影响知之甚少。为了确定 H2S 对骨代谢的可能生物活性，我们研究了 H2S 在脂多糖（LPS）和尼古丁刺激的人牙周韧带细胞（hPDLCs）中的体外细胞毒性、成骨细胞和破骨细胞分化的作用及其潜在机制。H2S 供体 NaHS 可防止 hPDLCs 受到尼古丁和 LPS 的细胞毒性，并恢复尼古丁和 LPS 下调的成骨细胞分化，如碱性磷酸酶（ALP）活性、成骨细胞的 mRNA 表达，包括 ALP、骨桥蛋白（OPN）和骨钙素（OCN）以及矿化结节形成。同时，NaHS 抑制了抗酒石酸酸性磷酸酶（TRAP）阳性破骨细胞在小鼠骨髓细胞中的分化，并阻断了尼古丁和 LPS 诱导的破骨细胞分化调节分子，如 RANKL、OPG、M-CSF、MMP-9、TRAP 和组织蛋白酶 K 的 mRNA。NaHS 阻断了尼古丁和 LPS 诱导的 p38、ERK、MKP-1、PI3K、PKC 和 PKC 同工酶以及 NF-κB 的激活。H2S 对尼古丁和 LPS 诱导的成骨细胞和破骨细胞分化的作用可被 MKP-1 酶抑制剂（钒酸盐）和表达抑制剂（雷公藤红素）显著逆转。综上所述，我们首次报道 H2S 可抑制细胞毒性和破骨细胞分化，并恢复尼古丁和牙周病原体刺激的 hPDLCs 模型中的成骨细胞分化，这对于治疗牙周炎和炎症性骨病具有潜在的治疗价值。
