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Molecular Advances in Metabolic Bone Disorders

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: 31 August 2026 | Viewed by 241

Special Issue Editor


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Guest Editor
Blood Sciences, South Tees Hospitals NHS Foundation Trust, Middlesbrough TS4 3BW, UK
Interests: metabolic bone disease; osteoporosis; molecular biology; bone cells; calciotropic factors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabolic bone disorders (MBD) can affect anyone but are more likely to occur in certain individuals, such as those with advanced age, vitamin D deficiency, chronic oral glucocorticoid use, acute weight loss, inactivity and alcohol excess. However, this issue of the journal is focused on rare metabolic disease. This is diverse group of disorders and include Paget's disease of bone (PDB), tumour-induced osteomalacia, fibrous dysplasia, osteogenesis imperfecta (OI), X-linked hypophosphatemia, hypophosphatasia (ALPL) and osteopetrosis. Healthy bone has a finely balanced remodelling coupling of formation by osteoblasts and resorption by osteoclast, normal mineralisation process and bone matrix formation. MBD have shared pathological features in collagen organisation, excess or abnormal osteoid or excess microfractures due to poor bone microarchitecture.

Regarding MBD, genetic and locus heterogeneity in various disorders, such as OI, ALPL and hypophosphatemic rickets, remains a challenge in linking phenotypic manifestation with molecular and cellular biology. The underlying molecular mechanism of somatic mosaicism remains a mystery for segmental PDB and mosaic OI. A deeper understanding of molecular biology of BMD is critical for explaining unpredictable severity of the disorders, early diagnosis and pathway-targeted therapies, as well as for future gene-editing and miRNA therapies.

Dr. Harish K. Datta
Guest Editor

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Keywords

  • metabolic bone disease
  • bone cells
  • rare diseases
  • genetics
  • molecular biology
  • skeletal development disorders

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Published Papers (1 paper)

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Research

27 pages, 18729 KB  
Article
Wolffia globosa Ethanolic Extract Protects Against Bisphenol A-Induced Osteoblast Dysfunction via Antioxidant Defense, Apoptosis Inhibition, and β-Catenin Modulation
by Benjawan Wudtiwai, Pornsiri Pitchakarn, Piya Temviriyanukul, Pattaralawan Sittiju, Woorawee Inthachat, Jirarat Karinchai, Nuttida Phunsanit, Prachya Kongtawelert and Peraphan Pothacharoen
Int. J. Mol. Sci. 2026, 27(12), 5352; https://doi.org/10.3390/ijms27125352 (registering DOI) - 13 Jun 2026
Abstract
The prevalent endocrine disruptor bisphenol A (BPA) is associated with aging-related conditions, including metabolic disorders. It has been shown that BPA promotes bone fragility through oxidative stress-induced apoptosis and impaired osteoblast differentiation. The identification of sustainable bioactive substances that alleviate BPA-induced bone toxicity [...] Read more.
The prevalent endocrine disruptor bisphenol A (BPA) is associated with aging-related conditions, including metabolic disorders. It has been shown that BPA promotes bone fragility through oxidative stress-induced apoptosis and impaired osteoblast differentiation. The identification of sustainable bioactive substances that alleviate BPA-induced bone toxicity is thus of biomedical and environmental significance. Wolffia globosa (WG), the world’s smallest flowering aquatic plant, has recently gained attention as a high-protein, antioxidant-rich nutraceutical, yet its impact on BPA-induced osteoblast dysfunction has not been systematically investigated. This study presents a comprehensive assessment of WG ethanolic extract (WGE) in MC3T3-E1 pre-osteoblasts, incorporating thorough phytochemical characterization, acute high-dose and chronic low-dose BPA exposure models, and multi-faceted mechanistic analysis. LC-MS/MS profiling identified luteolin (116.17 ± 0.69 µg/g), rosmarinic acid (54.80 ± 2.12 µg/g), and apigenin (48.77 ± 0.61 µg/g) as the predominant bioactive compounds. WGE exhibited potent antioxidant capacity across DPPH and ABTS radical scavenging assays, complemented by high ORAC and FRAP values, reflecting broad-spectrum antioxidant mechanisms. Treatment with WGE (25 and 50 µg/mL) resulted in significant alleviation of BPA-induced cytotoxicity, decreased intracellular ROS levels, and inhibited apoptosis. WGE (12.5 µg/mL) also modulated autophagy-related markers (LC3-II, Beclin-1, and p62), suggesting potential autophagic participation, although flux verification was not conducted. Treatment with WGE (12.5 µg/mL) also restored BPA-suppressed osteogenesis under chronic exposure, as evidenced by enhanced alkaline phosphatase activity, and increased both mineralization and upregulation of osteogenic genes including runt-related transcription factor2 (Runx2), collagen type I alpha 1 (Colla1), alkaline phosphatase (ALP), and osteocalcin (OCN). These effects were accompanied by partial reactivation of Wnt/β-catenin signaling. This study is the first to demonstrate that WGE protects osteoblasts from BPA toxicity by concurrently strengthening antioxidant defenses, limiting apoptosis, modulating autophagy-related markers, and supporting β-catenin-mediated osteogenesis, highlighting WG as a promising sustainable nutraceutical candidate for the prevention of environmental toxin-related bone fragility. Full article
(This article belongs to the Special Issue Molecular Advances in Metabolic Bone Disorders)
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