Lidocaine inhibits osteogenic differentiation of human dental pulp stem cells in vitro

Objective Lidocaine is an amide local anaesthetic commonly used for pain control, however, few studies have investigated the effect of lidocaine on the osteogenic differentiation of human dental pulp stem cells (HDPSCs). The present study aimed to determine the effect of lidocaine on HDPSC viability and osteogenic differentiation. Methods HDPSCs were incubated with 0, 0.05, 0.2, 0.5, and 1 mM lidocaine for 24, 48 and 72 h, after which, MTT assays were performed. HDPSCs cultured with the above lidocaine concentrations and osteogenic differentiation medium for 7 and 14 days were stained for alkaline phosphatase (ALP). Protein and mRNA levels of relevant osteogenic factors (bone morphogenetic protein-2 [BMP-2] and runt-related transcription factor 2 [RUNX2]) were examined using western blotting and real-time reverse-transcription polymerase chain reaction, respectively. Results Lidocaine did not affect the viability of HDPSCs, however, lidocaine reduced ALP activity in HDPSCs. Levels of ALP, BMP-2, and RUNX2 mRNA were reduced with lidocaine, and levels of BMP-2 and RUNX2 proteins were decreased, versus controls. Conclusions Lidocaine inhibits osteogenic differentiation markers in HDPSCs in vitro, even at low concentrations, without cytotoxicity. This study suggests that lidocaine may inhibit osteogenic differentiation in HDPSC-mediated regenerative medicine, including pulp regeneration and repair.

[1]  M. Hatta,et al.  Molecular mechanisms of lidocaine , 2021, Annals of medicine and surgery.

[2]  S. Patil,et al.  Effect of Ascorbic Acid on Differentiation, Secretome and Stemness of Stem Cells from Human Exfoliated Deciduous Tooth (SHEDs) , 2021, Journal of personalized medicine.

[3]  S. Patil,et al.  Parathyroid Hormone Secretion and Receptor Expression Determine the Age-Related Degree of Osteogenic Differentiation in Dental Pulp Stem Cells , 2021, Journal of personalized medicine.

[4]  J. Wrana,et al.  A novel negative regulatory mechanism of Smurf2 in BMP/Smad signaling in bone , 2020, Bone Research.

[5]  Y. Liu,et al.  Dental Tissue-Derived Human Mesenchymal Stem Cells and Their Potential in Therapeutic Application , 2020, Stem cells international.

[6]  A. Dietz,et al.  Differences in Cytotoxicity of Lidocaine, Ropivacaine, and Bupivacaine on the Viability and Metabolic Activity of Human Adipose-Derived Mesenchymal Stem Cells , 2020, American journal of physical medicine & rehabilitation.

[7]  Borong Huang,et al.  Alternative splicing in mesenchymal stem cell differentiation , 2020, Stem cells.

[8]  Ying Xue,et al.  DJ-1 plays a neuroprotective role in SH-SY5Y cells by modulating Nrf2 signaling in response to lidocaine-mediated oxidative stress and apoptosis. , 2020, The Kaohsiung journal of medical sciences.

[9]  G. Domańska,et al.  The Impact of Lidocaine on Adipose-Derived Stem Cells in Human Adipose Tissue Harvested by Liposuction and Used for Lipotransfer , 2020, International journal of molecular sciences.

[10]  Jin Liu,et al.  A review of the mechanism of the central analgesic effect of lidocaine , 2020, Medicine.

[11]  J. Mao,et al.  Pulp stem cells derived from human permanent and deciduous teeth: Biological characteristics and therapeutic applications , 2020, Stem Cells Translational Medicine.

[12]  T. Piegeler,et al.  Molecular mechanisms of action of systemic lidocaine in acute and chronic pain: a narrative review. , 2019, British journal of anaesthesia.

[13]  Qing Luo,et al.  Mesenchymal Stem Cell Migration and Tissue Repair , 2019, Cells.

[14]  A. Vercelli,et al.  Mesenchymal Stem Cells for Spinal Cord Injury: Current Options, Limitations, and Future of Cell Therapy , 2019, International journal of molecular sciences.

[15]  Xiaoning He,et al.  L‐type voltage‐gated calcium channels in stem cells and tissue engineering , 2019, Cell proliferation.

[16]  T. Komori Regulation of Proliferation, Differentiation and Functions of Osteoblasts by Runx2 , 2019, International journal of molecular sciences.

[17]  K. Paterson,et al.  Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. , 2019, Regenerative medicine.

[18]  John H. Zhang,et al.  Transplanting Mesenchymal Stem Cells for Treatment of Ischemic Stroke , 2018, Cell transplantation.

[19]  Yangzheng Li,et al.  Cytotoxicity of local anesthetics on rabbit adipose-derived mesenchymal stem cells during early chondrogenic differentiation , 2018, Experimental and therapeutic medicine.

[20]  I. Mortada,et al.  Dental pulp stem cells and osteogenesis: an update , 2018, Cytotechnology (Dordrecht).

[21]  Y. Ariji,et al.  Pulp regeneration by transplantation of dental pulp stem cells in pulpitis: a pilot clinical study , 2017, Stem Cell Research & Therapy.

[22]  Giorgio Mori,et al.  Vitamin D Effects on Osteoblastic Differentiation of Mesenchymal Stem Cells from Dental Tissues , 2016, Stem cells international.

[23]  H. Gou,et al.  Lidocaine inhibits the invasion and migration of TRPV6-expressing cancer cells by TRPV6 downregulation. , 2016, Oncology letters.

[24]  D. Agrawal,et al.  Key transcription factors in the differentiation of mesenchymal stem cells. , 2016, Differentiation; research in biological diversity.

[25]  Alan Trounson,et al.  Stem Cell Therapies in Clinical Trials: Progress and Challenges. , 2015, Cell stem cell.

[26]  M. Berry,et al.  Stem cell treatment of degenerative eye disease☆ , 2015, Stem cell research.

[27]  P. Angele,et al.  Local anesthetic cytotoxicity on human mesenchymal stem cells during chondrogenic differentiation , 2015, Knee Surgery, Sports Traumatology, Arthroscopy.

[28]  Yaqing Zhang,et al.  LPS Promote the Odontoblastic Differentiation of Human Dental Pulp Stem Cells via MAPK Signaling Pathway , 2015, Journal of cellular physiology.

[29]  J. Pacherník,et al.  Alkaline Phosphatase in Stem Cells , 2015, Stem cells international.

[30]  J. Rascon,et al.  Quick and effective method of bone marrow mesenchymal stem cell extraction , 2014, Open medicine.

[31]  C. Centeno,et al.  Amide‐Type Local Anesthetics and Human Mesenchymal Stem Cells: Clinical Implications for Stem Cell Therapy , 2014, Stem cells translational medicine.

[32]  Hubert T. Kim,et al.  Cytotoxicity of local anesthetics on human mesenchymal stem cells. , 2013, The Journal of bone and joint surgery. American volume.

[33]  S. Colucci,et al.  Dental pulp stem cells: osteogenic differentiation and gene expression , 2011, Annals of the New York Academy of Sciences.

[34]  Gui-Rong Li,et al.  Functional ion channels in stem cells. , 2011, World journal of stem cells.

[35]  Scott Hollister,et al.  Tissue formation and vascularization in anatomically shaped human joint condyle ectopically in vivo. , 2009, Tissue engineering. Part A.

[36]  M. Chancellor,et al.  In vitro and in vivo effect of lidocaine on rat muscle-derived cells for treatment of stress urinary incontinence. , 2009, Urology.

[37]  H. Roca,et al.  BMP Signaling Is Required for RUNX2‐Dependent Induction of the Osteoblast Phenotype , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[38]  J. Westendorf,et al.  Runx2: a master organizer of gene transcription in developing and maturing osteoblasts. , 2005, Birth defects research. Part C, Embryo today : reviews.

[39]  G. Sukhikh,et al.  Mesenchymal Stem Cells , 2002, Bulletin of Experimental Biology and Medicine.