2. Academic Validation
  3. MMP-1 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via the JNK and ERK pathway

MMP-1 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via the JNK and ERK pathway

  • Int J Biochem Cell Biol. 2020 Dec;129:105880. doi: 10.1016/j.biocel.2020.105880.
Yizhen Wu 1,  Yi Tang 2,  Xiaozhen Zhang 3,  Zhuangzhuang Chu 1,  Yajing Liu 1,  Chunbo Tang 4
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, PR China.
  • 2 Second Dental Center, School and Hospital of Stomatology, Peking University, Beijing, 100081, PR China.
  • 3 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, PR China; Department of Dental Implantology, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210029, PR China.
  • 4 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, PR China; Department of Dental Implantology, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210029, PR China. Electronic address: cbtang@njmu.edu.cn.
PMID: 33157237 DOI: 10.1016/j.biocel.2020.105880
Abstract

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.

Keywords

BMSCs; ERK pathway; JNK pathway; MMP-1; Osteogenic differentiation.

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