Engrailed 1: Effects of silencing and overexpression in mesenchymal stem cells, osteoblasts and osteocytes

• Grant number: 25/15142-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: December 01, 2025
• End date: October 31, 2030
• Field of knowledge: Health Sciences - Dentistry - Oral and Maxillofacial Surgery
• Principal Investigator: Adalberto Luiz Rosa
• Grantee: Thamires Mazzola
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 23/06782-2 - Participation of Engrailed 1 protein in differentiation of bone cells, skeletal growth, bone regeneration and osseointegration of titanium implants, AP.TEM

Abstract

The protein engrailed 1 (EN1) is a transcription factor distinguished by a DNA-binding domain known as homeobox. Changes in its expression lead to developmental and ossification abnormalities in certain bones. Given the crucial role of En1 in osteogenesis, we propose that En1 plays a part in bone cell differentiation. To test this hypothesis, we will examine the effects of En1 loss and gain of function in mesenchymal stem cells (MSCs), osteoblasts, and osteocytes. Using CRISPR technology, we will assess the impact of En1 silencing and overexpression in MSCs, osteoblasts, and osteocytes, evaluating parameters relevant to MSC characterization and the differentiation of osteoblastic and osteocytic cells. Numerical data will be subjected to a normal curve adherence test to determine the appropriate statistical analysis, with the significance level set at 5%. The results of this project will deepen the understanding of the molecular and cellular mechanisms by which En1 affects bone cells and osteogenesis, potentially leading to new therapies for promoting bone regeneration and osseointegration in challenging sites. These findings could have applications in Oral and Maxillofacial Surgery, Periodontics, Implantology, and Orthopedics. (AU)