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Molecular Mechanisms and Therapeutic Targets in Bone Biology and Cancer

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 January 2027 | Viewed by 1873

Editor


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Guest Editor
Department of Genomic Medicine, Instituto Nacional de Rehabilitacion, Calz México-Xochimilco 289, Mexico City 14389, Mexico
Interests: human genetics; osteoporosis; bone biology; bone cancer; vitamin D

Special Issue Information

Dear Colleagues,

Bone development involves interaction of genetic and environmental factors and is a dynamic process across one’s lifespan. This Special Issue seeks to gather recent advances to unravel the complexity of cellular pathways and networks affecting bone health. In this Special Issue, groundbreaking knowledge related to the molecular mechanisms underlying bone biology will be presented. In addition, readers can find research that provides insights into neoplastic transformation and progression into malignant lesions. Finally, this Special Issue will point out novel potential factors and molecules with clinical value for early diagnosis, therapeutic approaches and follow up of patients. Altogether, the information provided herein will also prompt future research with the aim of improving the current clinical management available for the patients affected by bone cancer.

Dr. Alberto Hidalgo-Bravo
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.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 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

  • bone health
  • molecular mechanisms
  • cancer biology
  • bone cancer
  • cancer therapeutics

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Published Papers (2 papers)

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Research

16 pages, 5885 KB  
Article
Telomeric DNA–Promyelocytic Leukemia (TEL–PML) Colocalization as an ALT Proxy in Relation to Metastatic Behavior in Osteosarcoma: A Retrospective Cohort Study
by Rogelio Frank Jiménez-Ortega, Rosa M. Salgado, Berenice Rivera-Paredez, Nelly Patiño, Tania Hilario-Huerta, Silvia Arenas-Díaz, Rafael Velázquez-Cruz and Alberto Hidalgo-Bravo
Curr. Issues Mol. Biol. 2026, 48(6), 553; https://doi.org/10.3390/cimb48060553 - 25 May 2026
Viewed by 601
Abstract
Osteosarcoma is the most common primary bone tumor in children, adolescents, and young adults, and metastasis remains the main determinant for a poor outcome. We conducted an exploratory retrospective cohort study using formalin-fixed, paraffin-embedded tissue from 97 patients with histopathologically confirmed osteosarcoma treated [...] Read more.
Osteosarcoma is the most common primary bone tumor in children, adolescents, and young adults, and metastasis remains the main determinant for a poor outcome. We conducted an exploratory retrospective cohort study using formalin-fixed, paraffin-embedded tissue from 97 patients with histopathologically confirmed osteosarcoma treated between 2005 and 2019 to evaluate telomere maintenance mechanisms. To assess alternative lengthening of telomeres (ALT), colocalization of telomeric DNA and promyelocytic leukemia protein (TEL–PML) was evaluated as a tissue-based proxy. TEL–PML colocalization was assessed using combined PML immunofluorescence and telomere DNA PNA-FISH. Furthermore, telomerase reverse transcriptase (TERT) expression was evaluated by immunohistochemistry in relation to metastasis and disease progression. Logistic regression models were adjusted for age, sex, and smoking. TEL–PML was evaluable in 45/97 cases, including 10 positive and 35 negative tumors; the remaining samples were non-evaluable because of non-determinable signal or predominant necrosis. TERT immunohistochemistry was scorable in 58/97 cases, of which 33 were positive. TEL–PML evaluability was associated with amputation specimens, whereas TERT positivity was associated with non-osteoblastic histology and was inversely associated with age. Neither TEL–PML nor TERT was significantly associated with metastasis, recurrence, or death. Exploratory time-to-metastasis curves suggested an earlier increase of metastatic events among TEL–PML-positive cases. However, the small number of positive tumors precludes definitive prognostic interpretation. These hypothesis-generating findings indicate that TEL–PML assessment is feasible in osteosarcoma, but it is strongly influenced by tissue adequacy. On the other hand, TERT immunohistochemistry appears to reflect subtype- and age-related heterogeneity rather than providing robust outcome stratification in this cohort. Full article
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16 pages, 5220 KB  
Article
Dual Inhibition of GSK3 and JAK by BIO Suppresses Osteoblast Differentiation and Mineralization of Human Mesenchymal Cells
by Nihal Almuraikhi, Latifa Alkhamees, Sumaiya Tareen and Manikandan Muthurangan
Curr. Issues Mol. Biol. 2026, 48(3), 316; https://doi.org/10.3390/cimb48030316 - 16 Mar 2026
Cited by 1 | Viewed by 941
Abstract
Glycogen synthase kinase-3 (GSK3) inhibition is a commonly used approach to promote osteogenic differentiation through activation of Wnt signaling. However, 6-bromoindirubin-3′-oxime (BIO), which is commonly used for GSK3 inhibition, also targets JAK/STAT, raising the possibility of dual pathway interference during osteoblast differentiation, as [...] Read more.
Glycogen synthase kinase-3 (GSK3) inhibition is a commonly used approach to promote osteogenic differentiation through activation of Wnt signaling. However, 6-bromoindirubin-3′-oxime (BIO), which is commonly used for GSK3 inhibition, also targets JAK/STAT, raising the possibility of dual pathway interference during osteoblast differentiation, as both GSK3 and JAK/STAT pathways are critical regulators of osteoblastogenesis. In this study, we investigated the effect of BIO on the osteoblast differentiation of hMSCs-TERT4. While BIO had no significant effect on cell viability or apoptosis, it markedly inhibited osteoblast differentiation, as evidenced by reduced ALP activity, decreased matrix mineralization, and downregulation of osteoblast-associated markers. Microarray analysis followed by qRT-PCR validation revealed downregulation of Wnt and TGF-β pathway genes. These findings show that BIO suppresses osteoblast commitment and osteogenic differentiation, accompanied by altered Wnt- and TGF-β-related gene expression. This study provides mechanistic insight into the off-target consequences of widely used small molecules and highlights the importance of dissecting pathway-specific roles in stem cell differentiation. Understanding the interplay between GSK3 and JAK signaling is essential for optimizing pharmacological strategies in skeletal regenerative medicine. This study highlights the importance of pathway selectivity when using small molecules in stem cell-based therapies for bone regeneration. Full article
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