Unveiling the Role of GH and IGF-1 in Regulating Collagen Synthesis in Tendons: A Study with Transgenic Mice.

• Grant number: 24/15956-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Diego Pulzatto Cury
• Grantee: Karoline dos Prazeres Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Tendons are composed of dense fibrous connective tissue, primarily made up of tenoblasts and tenocytes, which represent 90-95% of the cells. The extracellular matrix (ECM) of tendons is rich in collagen, with type I being the most abundant, providing mechanical strength, while type III, present in smaller quantities, plays a key role in tissue repair. Factors such as age, hormonal changes, and injuries alter the collagen ratio, leading to an increase in type III, which weakens the tendon. The incidence of tendinopathies increases with aging, affecting millions of people worldwide. GH and IGF-1, hormones that act on the ECM, stimulate cell proliferation and collagen synthesis. However, the individual role of each hormone in collagen synthesis remains unclear. Therefore, the current project aims to investigate, using transgenic mice, the specific role of GH and IGF-1 in the synthesis and maintenance of collagen in tendon tissue. Materials and Methods: Three genetically modified mouse models will be used: bGH mice, which have elevated circulating levels of GH and IGF-1; little/little mice, deficient in both GH and IGF-1; and Albumin¿GHR mice, which have normal or slightly increased GH levels but insignificant IGF-1 levels, allowing for the dissociation of GH from IGF-1. Wild-type C57BL/6 mice will be used as controls. Scanning electron microscopy will be employed for morphological analysis of the collagen fibers in the Achilles tendon, along with the evaluation of gene and protein expressions of type I and III collagen, remodeling markers MMP-1, -13, TIMP1, and 2, and the JAK/STAT and PI3K/Akt signaling pathways.