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Pharmacol Rep. 2018 Feb;70(1):29-36. doi: 10.1016/j.pharep.2017.07.006. Epub 2017 Jul 15.

Effect of acetaminophen on osteoblastic differentiation and migration of MC3T3-E1 cells.

Author information

1
Division of Dental Anesthesiology, Department of Control of Physical Functions, Kyushu Dental University, Kitakyushu, Japan; Division of Applied Pharmacology, Department of Health Promotion, Kyushu Dental University, Kitakyushu, Japan.
2
Division of Applied Pharmacology, Department of Health Promotion, Kyushu Dental University, Kitakyushu, Japan.
3
Division of Dental Anesthesiology, Department of Control of Physical Functions, Kyushu Dental University, Kitakyushu, Japan.
4
Division of Applied Pharmacology, Department of Health Promotion, Kyushu Dental University, Kitakyushu, Japan. Electronic address: r12takeuchi@fa.kyu-dent.ac.jp.

Abstract

BACKGROUND:

N-acetyl-p-aminophenol (APAP, acetaminophen, paracetamol) is a widely used analgesic/antipyretic with weak inhibitory effects on cyclooxygenase (COX) compared to non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism of action of APAP is mediated by its metabolite that activates transient receptor potential channels, including transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) or the cannabinoid receptor type 1 (CB1). However, the exact molecular mechanism and target underlying the cellular actions of APAP remain unclear. Therefore, we investigated the effect of APAP on osteoblastic differentiation and cell migration, with a particular focus on TRP channels and CB1.

METHODS:

Effects of APAP on osteoblastic differentiation and cell migration of MC3T3-E1, a mouse pre-osteoblast cell line, were assessed by the increase in alkaline phosphatase (ALP) activity, and both wound-healing and transwell-migration assays, respectively.

RESULTS:

APAP dose-dependently inhibited osteoblastic differentiation, which was well correlated with the effects on COX activity compared with other NSAIDs. In contrast, cell migration was promoted by APAP, and this effect was not correlated with COX inhibition. None of the agonists or antagonists of TRP channels and the CB receptor affected the APAP-induced cell migration, while the effect of APAP on cell migration was abolished by down-regulating TRPV4 gene expression.

CONCLUSION:

APAP inhibited osteoblastic differentiation via COX inactivation while it promoted cell migration independently of previously known targets such as COX, TRPV1, TRPA1 channels, and CB receptors, but through the mechanism involving TRPV4. APAP may have still unidentified molecular targets that modify cellular functions.

KEYWORDS:

Acetaminophen; Cyclooxygenase; Migration; Osteoblast; Transient receptor potential

PMID:
29306760
DOI:
10.1016/j.pharep.2017.07.006
[Indexed for MEDLINE]

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