Topical Application of Butyl Flufenamate Ointment Promotes Cranial Defect Healing in Mice by Inducing BMP2 Secretion in Skin Mesenchymal Stem Cells

Cells. 2022 Nov 15;11(22):3620. doi: 10.3390/cells11223620.

Abstract

Bone defects and fractures heal slowly compared with injuries to other tissues, creating a heavy burden for patients, their families, and society. Alongside conventional treatment methods for fractures and bone defects, adjuvant therapies play an important but underappreciated role. In a previous study, we found that systemic administration of flufenamic acid promoted osteogenesis in vivo, but its side effects limited the application of our findings. In the present study, we assess the effects of external butyl flufenamate ointment on the healing of cranial defects in mice. We found that application of butyl flufenamate ointment on the surface of the skin accelerated the healing of cranial defects in mice by promoting BMP2 secretion from mouse-skin mesenchymal stem-cells. These findings indicate that butyl flufenamate ointment has potential therapeutic value for treating superficial fractures or bone defects while avoiding the toxicity and side effects of systemic medication, representing a safe and convenient adjuvant therapy to promote healing of superficial bone defects and fractures.

Keywords: BMP2; butyl flufenamate ointment; mouse cranial defect; mouse-skin mesenchymal stem cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / pharmacology
  • Bone Regeneration
  • Flufenamic Acid / pharmacology
  • Fractures, Bone* / drug therapy
  • Mesenchymal Stem Cells*
  • Mice
  • Ointments / pharmacology

Substances

  • ufenamate
  • Flufenamic Acid
  • Ointments
  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (No. 81970908 and No. 82170929 to Y.L. and No. 82100978 to XNL).