Anti-CSF1 monoclonal antibody, clone 3E20

Objective: The present study aimed to investigate the inhibitory effect of acetaminophen on apical root resorption during orthodontic tooth movement by controlling inflammation in the periodontal ligament and apical pulp tissue. Methods: Human periodontal ligament and pulp cells were subjected to 10 kPa of cyclic tensile force (CTF) in a Flexcell Strain Unit for 48 h. Then, 10 and 100 pM acetaminophen were added to the culture medium, and the expression of interleukin (IL)-1B, receptor activator of nuclear factor kappa-B ligand (RANKL), tumor necrosis factor (TNF)alpha, and colony stimulating factor 1 (CSF1) were evaluated. In an animal experiment, the upper first molars of 7-week-old rats were moved mesially by applying 10 g of orthodontic force. After 30 days of force application, the effects of acetaminophen on apical root resorption were examined. Results: In both the periodontal ligament and pulp cells, the expression levels of IL-1B, TNF alpha, RANKL, and CSF1 were significantly higher in the CTF-treated group than in the control group. However, the expression levels of these factors were decreased by acetaminophen administration. High expression of IL-1B, TNF alpha, RANKL, and CSF1 at the root apex were also detected immunohistochemically in rats after tooth movement, but were decreased by acetaminophen administration. In addition, the number of odontoclasts and the amount of apical root resorption were significantly decreased in the acetaminophen group. Importantly, no significant difference in tooth movement was observed between the acetaminophen and control groups. Conclusions: These results suggest that acetaminophen can reduce severe root resorption in the apex area without disturbing orthodontic tooth movement.

Introduction: Tenosynovial giant cell tumor (TGCT) is a benign clonal neoplastic proliferation arising from the synovium often causing pain, swelling, joint stiffness, and reduced quality of life. The optimal treatment strategy in patients with diffuse-type TGCT (dt-TGCT) is evolving. Surgery is the main treatment, with a high recurrence rate and surgery-related morbidity. Radiotherapy is associated with important side effects. TGCT cells overexpress colony-stimulating factor 1 (CSF1). Pexidartinib (Turalio (TM)) is a selective CSF1 R inhibitor, which was recently approved by the FDA for the treatment of TGCT. Areas covered: This article reviews the pharmacological properties, clinical efficacy, and safety of pexidartinib. Expert opinion: Pexidartinib was effective with an acceptable safety profile for advanced TGCT in phase I-III studies. The phase III trial (ENLIVEN) in unresectable TGCT met its primary endpoints of overall response rate. These results led to FDA approval for this TGCT population. Mixed or cholestatic hepatotoxicity was observed in rare cases. For this reason, pexidartinib is currently available only through a Risk Evaluation and Mitigation Strategy (REMS) Program in the USA. TGCT significantly impairs patients' quality of life. The approval of pexidartinib has changed the therapeutic armamentarium for this condition. However, strict monitoring of liver function is warranted.