Connecting Bone Remodeling and Regeneration: Unraveling Hormones and Signaling Pathways
by
, , , , and
Afshan Mehreen
1,2,
Muhammad Faisal
1,2,
Bilal Zulfiqar
3,
Deli Hays
1,2,
Kavishka Dhananjaya
1,2,
Faiza Yaseen
1,2 and
Yujun Liang
1,2,* 1
Key Laboratory of Evolution and Marine Biodiversity (Ministry of Education), Institute of Evolution and Marine Biodiversity, Ocean University of China, Qingdao 266003, China
2
College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China
3
Discovery Biology, Griffith University, Nathan, QLD 4111, Australia
*
Author to whom correspondence should be addressed.
Biology 2025, 14(3), 274; https://doi.org/10.3390/biology14030274
Submission received: 16 February 2025
/
Revised: 2 March 2025
/
Accepted: 5 March 2025
/
Published: 7 March 2025
(This article belongs to the Special Issue Tissue and Organ Regeneration in Fish: Evolutionary Mechanisms)
Simple Summary
Bone diseases and injuries often result in poor healing and long-lasting damage, affecting millions of people worldwide and highlighting the urgency for better treatments. Understanding the mechanisms of how to control the complex process of bone repair and regeneration without unwanted side effects, such as metabolic imbalances or excessive tissue growth, and translating knowledge from animal studies to humans has remained one of the major challenges. This literature review explores the intricate relationship between bone regeneration and bone remodeling, with a particular emphasis on the role of hormones and key molecular factors that may influence the regenerative capacity in model organisms. It examines the signaling pathways and molecular interactions that facilitate a seamless regeneration process. Key endocrine factors such as PTH, calcitonin, and FGF23 play crucial roles in bone remodeling and healing, with potential therapeutic applications. The review underscores both the opportunities and challenges of translating these findings into human regenerative medicine.
Abstract
Recent advancements in tissue engineering and stem cell science have positioned bone disease treatment as a promising frontier in regenerative medicine. This review explores the hormonal and signaling pathways critical to bone regeneration, with a focus on their clinical relevance. Key endocrine factors, including thyroid hormones (T3 and T4), insulin-like growth factor 1 (IGF-1), bone morphogenetic proteins (BMPs), parathyroid hormone (PTH), calcitonin, and fibroblast growth factor 23 (FGF23), play pivotal roles in bone remodeling by regulating osteoblast activity, bone resorption, and mineralization. These factors primarily act through the Wnt/β-catenin, BMP, and FGF signaling pathways, which govern bone repair and regeneration. While animal models, such as axolotls, zebrafish, and Xenopus laevis, provide valuable findings about these mechanisms, translating these findings into human applications presents challenges. This review underscores the therapeutic potential of modulating these hormonal networks to enhance bone regeneration while cautioning against possible adverse effects, such as uncontrolled tissue proliferation or metabolic imbalances. By integrating knowledge from regenerative models, this work provides a foundation for optimizing hormone-based therapies for clinical applications in bone repair and disease treatment.
Keywords:
regeneration; bone regeneration; bone remodeling; axolotl; zebrafish; hormones
