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Bone Development and Regeneration—4th Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 399

Special Issue Editor


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Guest Editor
Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki 216-8512, Japan
Interests: articular cartilage; chondrocytes; polychondritis
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Special Issue Information

Dear Colleagues,

The bone is a fascinating tissue conferring structural body support, mechanical integrity, and organ protection. A more holistic perspective sees the bone as an integral organ that, together with other tissues, not only regulates mineral homeostasis and maintains the hematopoietic niche but also plays endocrine functions, contributing to and regulating numerous metabolic processes independent of the mineral metabolism.

Bone formation is orchestrated by multiple stimuli and processes, and based on their embryological origin, the ossification of collagenous tissues is regulated by different paths. Compared to other musculoskeletal tissues, the bone has a high regenerative potential, with the skeleton being fully remodeled multiple times throughout the human lifespan. However, with a continuous extension of life expectancy, aging-related bone issues and pathologies have become more prominent, negatively impacting the quality of life of an increasing number of individuals.

While several mechanisms and pathways, such as the WNT, BMP2, or PTH signaling pathways, have been thoroughly studied over the last few decades, new scientific capabilities and perspectives allow for a more integrative and comprehensive view of bone development and regeneration. With the revolutionary rise of the omics field and the latest advances in cell lineage-tracing models and single-cell analysis, new molecular mechanisms are being elucidated, and important novel players are being recognized. For example, our understanding of epigenetic processes or metabolites that control bone integrity is growing at a rapid pace. In concert with the progress made recently in the development and design of new scaffolds and biomaterials, all these advances generate novel and alternative approaches to target bone regeneration and are under investigation, with the potential to increase the quality of life for many people.

This Special Issue of IJMS provides a platform for high-quality publications exploring novel insights on bone development and/or presenting new molecular and conceptual approaches for the manipulation of osteogenesis, bone regeneration, and bone homeostasis. This will provide a representative picture of the latest advances in bone research and serve as a road map for the future of the bone field.

Prof. Dr. Kazuo Yudoh
Guest Editor

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Keywords

  • osteoblast
  • osteocyte
  • osteoclast
  • mesenchymal stem cell
  • cell differentiation
  • epigenetics
  • omics
  • integrative analysis
  • biomaterials

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Published Papers (1 paper)

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Research

20 pages, 5374 KiB  
Article
Repetitive Compressive Loading Downregulates Mitochondria Function and Upregulates the Cartilage Matrix Degrading Enzyme MMP-13 Through the Coactivation of NAD-Dependent Sirtuin 1 and Runx2 in Osteoarthritic Chondrocytes
by Masahiro Takemoto, Yodo Sugishita, Yuki Takahashi-Suzuki, Hiroto Fujiya, Hisateru Niki and Kazuo Yudoh
Int. J. Mol. Sci. 2025, 26(11), 4967; https://doi.org/10.3390/ijms26114967 - 22 May 2025
Viewed by 274
Abstract
Mechanical stress is known to be a pivotal risk factor in the development of OA. However, the involvement of repetitive compressive loading in mitochondrial dysfunction in chondrocytes remains unclear. The aim of this study was to investigate whether physiologic levels of repetitive mechanical [...] Read more.
Mechanical stress is known to be a pivotal risk factor in the development of OA. However, the involvement of repetitive compressive loading in mitochondrial dysfunction in chondrocytes remains unclear. The aim of this study was to investigate whether physiologic levels of repetitive mechanical force affect the regulation of energy metabolism and activities of mitochondrial function regulators, sirtuin 1 and nicotinamide adenine dinucleotide (NAD) in chondrocytes, and to clarify any correlation with chondrocyte catabolic activity. Repetitive physiological mechanical stress was applied in a 3D chondrocyte-collagen scaffold construct, and the 3D cultured tissues were collected at different time points by collagenase treatment to collect cellular proteins. Changes in chondrocyte activity (cell proliferation, MMP-13 production), energy metabolism regulator levels (sirtuin 1), mitochondrial function (ATP production, NAD level), and the expression level of the osteogenic and hypertrophic chondrogenic transcription factor, runt-related transcription factor 2 (Runx2), were measured. Treatment with repetitive compressive loading resulted in no significant change in the cell viability of chondrocytes. In the repetitive mechanical loading group, there were statistically significant increases in MMP-13 production and expression of both sirtuin 1 and Runx2 in chondrocytes relative to the non-loading control group. Furthermore, ATP production and NAD activity in mitochondria decreased in the repetitive mechanical loading group. Our present study reveals that in chondrocytes, repetitive compressive loading accelerated sirtuin activation, which requires and consumes NAD within mitochondria, leading to a decrease of NAD and ultimately in reduced mitochondrial ATP production. Additionally, since sirtuin 1 is known to positively regulate Runx2 activity in chondrocytes, the activation of sirtuin 1 by repetitive load stimulation may induce an increase in the expression of Runx2, which promotes the expression of MMP-13, and subsequently enhances MMP-13 production. Our findings indicate that repetitive compression loading-mediated mitochondrial dysfunction plays a pivotal role in the progression of OA, primarily by driving the downregulation of ATP production and promoting the expression of the matrix-degrading enzyme MMP-13. Full article
(This article belongs to the Special Issue Bone Development and Regeneration—4th Edition)
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