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Advances in Molecular and Cellular Mechanisms in Metabolic Bone and...
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Advances in Molecular and Cellular Mechanisms in Metabolic Bone and Cartilage Disorders

A Special Issue of Biomedicines (ISSN 2227-9059) belonging to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 1473

Editor

Dr. Mohamad Alaa Terkawi

E-Mail Website
Guest Editor
Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15, Nish-7, Kita-ku, Sapporo 060-8638, Japan
Interests: osteolysis; inflammatory; neutrophils; macrophages; immune responses; bone resorption
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabolic bone and cartilage disorders are at the forefront of research connecting skeletal biology, metabolism, and chronic disease. For this Special Issue, we invite submissions that explore recent advances in the molecular and cellular mechanisms by which alterations in energy metabolism, endocrine regulation, and inflammatory signaling compromise bone integrity and joint function. Studies on osteoporosis, osteoarthritis, impaired fracture healing, and rare metabolic skeletal diseases are especially welcome, with emphasis on the pathways linking systemic and local metabolic imbalances to defective bone remodeling and cartilage degeneration. By bridging fundamental mechanistic insights with translational and clinical research, this Special Issue aims to illuminate the metabolic determinants of musculoskeletal health and inspire innovative approaches for disease prevention, early intervention, and therapy development.

Dr. Mohamad Alaa Terkawi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabolic bone
  • cartilage disorders
  • osteoporosis
  • osteoarthritis
  • impaired fracture healing
  • rare metabolic skeletal diseases

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Published Papers (2 papers)

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Research

23 pages, 8606 KB  
Article
Integrated Bulk and Single-Cell Transcriptomics Reveals the C3–C3AR1 Axis as a Candidate Mediator of Coagulome-Immune Crosstalk in Osteosarcoma
by Jianhua Mu, Yitian Wang, Han Liu, Xuanhong He, Zhuangzhuang Li, Minxun Lu, Fan Tang, Yi Luo, Yong Zhou, Li Min and Chongqi Tu
Biomedicines 2026, 14(8), 1686; https://doi.org/10.3390/biomedicines14081686 - 27 Jul 2026
Viewed by 438
Abstract
Background: Although the tumor coagulome interacts with the tumor immune microenvironment (TME) in solid tumors, its role in osteosarcoma (OS) remains uncharacterized. This study aimed to delineate this transcriptomic interplay and identify potential prognostic targets. Methods: This study was performed with bulk RNA [...] Read more.
Background: Although the tumor coagulome interacts with the tumor immune microenvironment (TME) in solid tumors, its role in osteosarcoma (OS) remains uncharacterized. This study aimed to delineate this transcriptomic interplay and identify potential prognostic targets. Methods: This study was performed with bulk RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), and clinical phenotype data. Bioinformatic approaches were employed at the transcriptomic level to investigate the impact of the tumor coagulome on the TME and prognosis in OS. We validated the above findings using immunohistochemistry and immunofluorescence. Results: The activity of a coagulation-related transcriptional signature was found to correlate with the degree of malignancy in OS. Its activity score demonstrated predictive value for OS prognosis, with a maximum area under the curve (AUC) of 0.802. scRNA-seq analysis indicated that inflammatory cancer-associated fibroblasts (iCAFs) and APOE+ macrophages were predominantly enriched in the high coagulation score subgroup. Our data further suggest that iCAFs may facilitate the M2 polarization of APOE+ macrophages via the C3–C3AR1 axis, potentially contributing to poorer clinical outcomes in patients with OS. Conclusions: These findings imply that within a high coagulation-related transcriptional score group, the interaction between iCAFs and APOE+ macrophages, likely mediated by the C3–C3AR1 axis, could facilitate OS progression. Consequently, the C3–C3AR1 signaling pathway might represent a promising target for future therapeutic strategies and coagulome monitoring in OS. Full article
(This article belongs to the Special Issue Advances in Molecular and Cellular Mechanisms in Metabolic Bone and Cartilage Disorders)
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16 pages, 4039 KB  
Article
Genetic Diversity Analysis of Risk Variants Associated with Bone and Cartilage Metabolism in Nine Mexican Subpopulations
by Ismael Nuño-Arana, Alejandra Villagómez Vega and Gabriela Martínez Cortés
Biomedicines 2026, 14(7), 1470; https://doi.org/10.3390/biomedicines14071470 - 29 Jun 2026
Viewed by 505
Abstract
Backgrounds/Objectives: Allele frequencies of genetic variants associated with complex diseases can contribute to varying degrees to predisposition depending on the population’s genetic profile. The aim of this study was to analyze the genetic diversity of 15 relevant SNVs that could modulate bone and [...] Read more.
Backgrounds/Objectives: Allele frequencies of genetic variants associated with complex diseases can contribute to varying degrees to predisposition depending on the population’s genetic profile. The aim of this study was to analyze the genetic diversity of 15 relevant SNVs that could modulate bone and cartilage metabolism in underrepresented structured populations. Methods: In a sample of 130 Mestizos and 304 natives from 8 native Mexican populations, SNVs related to multifactorial diseases were genotyped using a SNaPShot Multiplex kit and analyzed via capillary electrophoresis using an ABI PrismTM 3130 Genetic Analyzer (Applied Biosystems, Waltham, MA, USA.), and genetic profiles for 15 SNVs were obtained using GeneMapper software v. 3.2. Allele frequencies were calculated by locus and population using Power Stats and Arlequin v.3.1 software, for which the EM algorithm was used to compare reference populations obtained from the dbSNV database of the International HapMap project. Population structure, paired comparisons, and genetic differentiation between native, admixed, and reference populations (p value) were estimated through Fst tests using the STRUCTURE v.2.3.2 and Arlequin v.3.1 software. Results: Haplotype frequency combinations grouped as profiles showed higher predominance in the allelic combination A/A/G for rs9340799 (ESR1), rs700518 (CYP19A1), and rs1800795 (IL6) genes, respectively. Conclusions: Allelic profiles could be useful as medical tools for preventing and managing individuals or populations. Mexican populations showed high genetic variability among allelic risk profiles for estrogen control and response, as well as high frequencies of variant combinations associated with an increased inflammatory response, potentially resulting in high osteoclastogenesis. This analysis advances our understanding of the complexity of bone and cartilage metabolism in highly stratified populations. Full article
(This article belongs to the Special Issue Advances in Molecular and Cellular Mechanisms in Metabolic Bone and Cartilage Disorders)
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