Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, PR China.
Second Dental Center, School and Hospital of Stomatology, Peking University, Beijing, 100081, PR China.
Int J Biochem Cell Biol. 2020 Dec;129:105880. doi: 10.1016/j.biocel.2020.105880. Epub 2020 Nov 4.
Enhancing the functions of mesenchymal stem cells (MSCs) is considered a potential approach for promoting tissue regeneration. In this study, we investigated the effects of Matrix Metalloproteinase-1 (MMP-1) on bone marrow mesenchymal stem cells (BMSCs) and its mechanism. Our results showed that knockdown of MMP-1 impeded scratch closure, attenuated proliferation, inhibited ALP activity, ALP denser staining and mineralization in vitro, and decreased expression of RUNX2, OSX, OPN and OCN in BMSCs, while 20 ng/mL recombinant human MMP-1 protein (rhMMP-1) significantly accelerated scratch closure, enhanced proliferation, ALP activity, ALP denser staining and mineralization in vitro, and increased expression of RUNX2, OSX, OPN and OCN. In addition, knockdown of MMP-1 inhibited the expression of phosphorylated c-Jun N-terminal kinase (p-JNK) and phosphorylated extracellular regulated protein kinases (p-ERK), while 20 ng/mL rhMMP-1 increased the expression of p-JNK and p-ERK in BMSCs. Furthermore, inhibition of c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases (ERK) by their inhibitor SP600125 and PD98059 dramatically blocked MMP-1-enhanced ALP activity and mineralization in BMSCs. Our results revealed that MMP-1 could accelerate the osteogenic differentiation potentials of BMSCs via the JNK and ERK pathway, providing the mechanism underlying MSC biology and identifying a potential target for improving bone tissue regeneration.
增强间充质干细胞（MSCs）的功能被认为是促进组织再生的一种有潜力的方法。在本研究中，我们研究了基质金属蛋白酶-1（MMP-1）对骨髓间充质干细胞（BMSCs）的影响及其机制。我们的结果表明，MMP-1 的敲低会阻碍划痕闭合，减弱增殖，抑制 ALP 活性、ALP 染色密度和体外矿化，降低 BMSCs 中 RUNX2、OSX、OPN 和 OCN 的表达，而 20ng/mL 重组人 MMP-1 蛋白（rhMMP-1）则显著加速划痕闭合，增强增殖、ALP 活性、ALP 染色密度和体外矿化，增加 RUNX2、OSX、OPN 和 OCN 的表达。此外，MMP-1 的敲低会抑制磷酸化 c-Jun N 端激酶（p-JNK）和磷酸化细胞外调节蛋白激酶（p-ERK）的表达，而 20ng/mL rhMMP-1 则增加了 BMSCs 中 p-JNK 和 p-ERK 的表达。此外，c-Jun N 端激酶（JNK）和细胞外调节蛋白激酶（ERK）抑制剂 SP600125 和 PD98059 显著抑制 MMP-1 增强的 BMSCs 中 ALP 活性和矿化。我们的结果表明，MMP-1 可以通过 JNK 和 ERK 通路加速 BMSCs 的成骨分化潜能，为 MSC 生物学提供了机制，并确定了改善骨组织再生的潜在靶点。
