Yujun Liang

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.

Hsp90, a critical molecular chaperone, is instrumental in modulating an array of signaling path-ways, transcription factors, and cytokines, with its overexpression intricately tied to the onset of tumorigenesis. While the modulation of Hsp90 holds potential for facilitating tissue regeneration, its functional implications in epimorphic regeneration remain largely uncharted. This study ex-plored the role of Hsp90 in tail regeneration in axolotls and compared it to its roles in other epi-morphic regeneration processes, such as tail fin regeneration in zebrafish and tail regeneration in amphioxus. Our findings indicated that Hsp90α, the inducible subtype of Hsp90, exhibited dis-tinctive and dynamic expression patterns throughout these regeneration processes. The knock-down of Hsp90α via morpholinos or the pharmacological inhibition of Hsp90 using geldanamycin following tail amputation in axolotls hindered regeneration. Similar phenotypes of failed regen-eration due to Hsp90 inhibition were also observed in zebrafish and amphioxus. Furthermore, cellular evidence suggested that the suppression of Hsp90 results in diminished cell proliferation and elevated apoptosis, partially accounting for the observed impairment in regeneration. RNA-seq analysis of Hsp90-inhibited and control axolotls and zebrafish provided deeper insights into the regulatory mechanism of Hsp90 in regeneration. Numerous differentially expressed genes identified are transcription factor genes or key signaling genes involved in cell proliferation, apoptosis, cancer development, and the immune response. These findings imply that Hsp90 is essential in epimorphic regeneration processes and its functional roles appear to be conserved among chordates as a pivotal regulator in the regeneration process.

The axolotl, a legendary creature with the potential to regenerate complex body parts, is positioned as a powerful model organism due to its extraordinary regenerative capabilities. Axolotl can undergo successful regeneration of multiple structures, providing us with the opportunity to understand the factors that exhibit altered activity between regenerative and non-regenerative animals. This comprehensive review will explore the mysteries of axolotl regeneration, from the initial cellular triggers to the intricate signaling cascades that guide this complex process. We will delve deeply into the multifaceted interplay of genes and factors, highlighting the key role of signaling pathways and the influence of epigenetic modifications (such as DNA methylation, histone modification, and miRNA regulation) during regeneration. Furthermore, we will discuss how axolotls defy the odds by showing remarkable resistance to cancer, offering insights into potential therapeutic strategies. However, that is not the end; we will also highlight how age might affect the regenerative power of this creature. We hope this review will help navigate the awe-inspiring realm of axolotl regeneration, advance our understanding of regenerative biology, and chart pathways for future investigations aimed at uncovering new therapeutic approaches.

Regeneration enables the regrowth and restoration of missing body parts. It is a common phenomenon among animals. However, only some species exhibit remarkable regeneration capabilities and can regenerate organs such as limbs, lenses or hearts. Regeneration has been widely studied, thereby giving rise to new fields, such as regenerative medicine. Furthermore, regeneration has the potential to be applied to the human body. However, the molecular mechanisms governing this process should be elucidated first. Recent advancements in research methods have led to the identification of numerous signaling pathways involved in regeneration. One of them, the Wnt transduction pathway, is an ancient and evolutionarily conserved pathway that plays an important role in both embryonic development and regeneration. The Wnt pathway plays an important role during the regeneration process, as it is implicated in cell fate determination, cell migration, cell polarity and adult cell homeostasis. To date, two major Wnt pathways have been identified: the canonical (β-catenin dependent) pathway and the non-canonical pathway. The latter pathway can be further divided into planar cell polarity, the Wnt/Ca2+ pathway and the JNK pathway. In this review, we summarize the current state of knowledge regarding the Wnt signaling pathway and its role in regeneration, with a particular emphasis on key model species.

Background Nile tilapia (Oreochromis niloticus), an important economic freshwater fish being cultured globally, is highly adaptable to a wide range of salinities. However, little information is currently available on the mechanism of salinity adaptation. Objective For a better understanding of this intriguing adaptability, we identified and analyzed aquaporins (AQPs), which are channel proteins with a basic function of intracellular and intercellular transportation for water and certain solutes. Methods In the present study, we performed genome-wide identification and comprehensive analysis of the duplicated AQP genes in Nile tilapia by bioinformatics methods. Tissue-specific analyses were then combined with transcriptome data under different salinity treatments. Results It was revealed that Nile tilapia has a total of twenty-eight AQPs, which are distributed unevenly on twelve chromosomes and belong to four subfamilies according to phylogenetic analysis. These AQPs share conserved AQP characteristic structural domains and motifs, although they differ in molecular weight from 23 to 36 kDa and contain distinct sequences. GO analysis revealed that most AQPs have transporter protein activity and are involved in biological processes such as substance transport, stress response, development and metabolism. KEGG enrichment analysis showed that AQPs were significantly enriched in two pathways, anti-diuretic hormone-regulated reabsorption and bile secretion. Conclusion These results suggested that Nile tilapia has a highly developed, albeit complex, osmotic pressure regulation system, which provided a molecular basis for exploring how these AQP members coordinate to help Nile tilapia cope with different salinities.

Among vertebrates, urodele amphibians possess a unique ability to regenerate various body parts including limbs. However, reports of their digit regeneration remain scarce, especially information about the related genes. In this study, it was evident that matrix metalloproteinases (mmps) including mmp9, mmp3/10a, and mmp3/10b, which play a crucial role in tissue remodeling, are highly expressed during early stages of digit regeneration in axolotl. Using in situ hybridization, we revealed that wound epidermis and blastema are two major origins of the MMPs during the regeneration process. Additionally, we found that the inhibition of MMPs with GM6001 (a wide-spectrum inhibitor of MMPs) in vivo after amputation disturbed normal digit regeneration process and resulted in malformed regenerates. Furthermore, inhibition of MMPs hindered blastema formation and decreased cell apoptosis at early stages in the digit regenerates. All these points suggest that MMPs are required for digit regeneration, as they play a significant role in the regulation of blastema formation.

Amphioxus, a cephalochordate, is an ideal animal to address the questions about the evolution of regenerative ability and mechanisms behind the invertebrate to vertebrate transition in chordates. However, the cellular and molecular basis of tail regeneration in amphioxus remains largely ill-defined. We confirmed that the tail regeneration of amphioxus Branchiostoma japonicum is a vertebrate-like epimorphosis process. We performed transcriptome analysis of the tail regenerates, which provided many clues for exploring the mechanism of tail regeneration. Importantly, we showed that BMP2/4 and its related signaling are essential for the process of tail regeneration, revealing an evolutionarily conserved genetic regulatory system involved in regeneration in many metazoans. We serendipitously discovered that, bmp2/4 expression is immediately inducible by general wounds and that the expression of bmp2/4 can be regarded as a biomarker of wounds in amphioxus. Collectively, our results provide a framework for understanding the evolution and diversity of cellular and molecular events of tail regeneration in vertebrates.