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Advances in Bone Growth, Development and Metabolism

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

Deadline for manuscript submissions: closed (20 January 2025) | Viewed by 14790

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Prof. Dr. Anna Charuta

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Guest Editor

Institute of Health, Faculty of Medical and Health Sciences, Siedlce University of Natural Sciences and Humanities, Konarskiego 2, 08-110 Siedlce, Poland
Interests: anatomy; histology; psychology; human sciences

Dr. Agnieszka Paziewska

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Guest Editor

Institute of Health Sciences, Faculty of Medical and Health Sciences, Siedlce University of Natural Sciences and Humanities, Konarskiego 2, 08-110 Siedlce, Poland
Interests: cancer pathogenesis; cancer therapy; cancer progression; tumor biomarker

Special Issue Information

Dear Colleagues,

The purpose of this Special Issue is to present the latest research Advances in Bone Growth, Development and Metabolism.

Bone tissue is a living, metabolically active tissue that plays a major role in regulating electrolyte concentrations in the body. Bone tissue is a metabolic depot of ions, mainly calcium, phosphorus and magnesium. Bone tissue and calcium homeostasis in the body depends on the balance of bone resorption and bone formation. Bone tissue undergoes remodeling during an individual's lifetime. Bone modeling continues throughout life with varying degrees of severity. It is dependent on hormones, mainly parathormone and calcitonin. In trabecular bone, the synthesis and resorption of bone tissue occur on the surface of the trabeculae. In the case of compact bone, internal bone remodeling consists of the resorption of bone tissue, followed by the formation of new Haversian systems.

This Special Issue invites researchers to submit original research papers and reviews on all aspects of bone metabolism. Topics of interest include, but are not limited to, the following: (1) anatomy and pathology of the skeletal system, including selected concepts from orthopedics, traumatology and rheumatology; (2) bone grafts, their properties, remodeling of bone grafts; (3) growth and modeling of bone tissue, bone tissue remodeling, biochemical markers of bone tissue remodeling (osteonectin, osteocalcin); (4) distology and histopathology of bone tissue; (5) basic studies of bone metabolism related to cell biology and molecular biology; (6) preclinical studies in metabolic diseases and bone homeostasis; (7) pathophysiology of metabolic bone diseases (osteoporosis); (8) disorders of the immune system in relation to bone tissue; (9) and genetic bone diseases.

Dr. Anna Charuta
Dr. Agnieszka Paziewska
Guest Editors

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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 100 words) can be sent to the Editorial Office for announcement on this website.

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-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

bone metabolism
osteoporosis
bone mineral density
postmenopausal women
bone marrow
osteoimmunology
magnetic resonance imaging
bone and bones
osteoporosis, postmenopausal* prevention and control
femur neck
osteomicrobiology
neuroskeletal biology
genetic background of bone diseases

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Published Papers (8 papers)

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21 pages, 3583 KiB

Open AccessArticle

Exploring a Nitric Oxide-Releasing Celecoxib Derivative as a Potential Modulator of Bone Healing: Insights from Ex Vivo and In Vivo Imaging Experiments

by Christin Neuber, Luisa Niedenzu, Sabine Schulze, Markus Laube, Frank Hofheinz, Stefan Rammelt and Jens Pietzsch

Int. J. Mol. Sci. 2025, 26(6), 2582; https://doi.org/10.3390/ijms26062582 - 13 Mar 2025

Viewed by 406

Abstract

The inducible enzyme cyclooxygenase-2 (COX-2) and the subsequent synthesis of eicosanoids initiated by this enzyme are important molecular players in bone healing. In this pilot study, the suitability of a novel selective COX-2 inhibitor bearing a nitric oxide (NO)-releasing moiety was investigated as a modulator of healing a critical-size bone defect in rats. A 5 mm femoral defect was randomly filled with no material (negative control, NC), a mixture of collagen and autologous bone fragments (positive control, PC), or polycaprolactone-co-lactide (PCL)-scaffolds coated with two types of artificial extracellular matrix (aECM; collagen/chondroitin sulfate (Col/CS) or collagen/polysulfated hyaluronic acid (Col/sHA3)). Bone healing was monitored by a dual-tracer ([¹⁸F]FDG/[¹⁸F]fluoride) approach using PET/CT imaging in vivo. In addition, ex vivo µCT imaging as well as histological and immunohistochemical studies were performed 16 weeks post-surgery. A significant higher uptake of [¹⁸F]FDG, a surrogate marker for inflammatory infiltrate, but not of [¹⁸F]fluoride, representing bone mineralization, was observed in the implanted PCL-scaffolds coated with either Col/CS or Col/sHA3. Molecular targeting of COX-2 with NO-coxib had no significant effect on tracer uptake in any of the groups. Histological and immunohistochemical staining showed no evidence of a positive or negative influence of NO-coxib treatment on bone healing. Full article

(This article belongs to the Special Issue Advances in Bone Growth, Development and Metabolism)

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18 pages, 4518 KiB

Open AccessArticle

Impact of Titanium Plate Fixation on Diacylglycerol and Growth Factor Levels in the Periosteum of the Mandible and Maxilla in Patients with Dentofacial Deformities After Jaw Osteotomies

by Bożena Antonowicz, Jan Borys, Kamila Roszczyc-Owsiejczuk, Kamila Łukaszuk, Anna Zalewska and Agnieszka U. Błachnio-Zabielska

Int. J. Mol. Sci. 2025, 26(5), 2020; https://doi.org/10.3390/ijms26052020 - 26 Feb 2025

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Abstract

Titanium is widely recognized for its biocompatibility and utility in maxillofacial and orthopedic surgery; however, its influence on bone remodeling biomarkers remains underexplored. This study investigates the effects of uncoated titanium plates on both the growth factors and diacylglycerols (DAGs) in the periostea of the maxilla and mandible, as DAG signaling is an essential secondary messenger molecule involved in intracellular signaling connected to various growth factors. The study group comprised 20 patients undergoing bimaxillary osteotomies using miniplates and screws made of Ti6Al4V titanium, from whom bone fixations were removed, while the control group included 20 patients operated on for dentofacial deformities (before the insertion of titanium fixations). Diacylglycerol levels in the serum and periosteum were analyzed using tandem mass spectrometry coupled with ultra-high performance liquid chromatography. Growth factors in the periosteum were measured via ELISA with commercially available assay kits. Our findings demonstrate a significant reduction in growth factors, including IGF-1, PDGF, and FGF-23, alongside decreased total DAG levels, suggesting titanium plate stabilization may modulate bone remodeling dynamics. Notably, while overall DAG levels declined, specific DAG species such as C16:0/16:0 and C18:0/18:0 were elevated, whereas polyunsaturated DAGs showed reductions, indicating selective regulation of lipid signaling pathways. Correlation analyses highlighted complex interactions between growth factors and DAGs, with distinct regional differences observed in the mandibular and maxillary periostea. These alterations may result from chronic titanium exposure, potentially inducing a low-grade immune response or modifying the local biochemical environment. This study emphasizes the need for further research into the long-term effects of titanium implants, particularly their influence on lipid metabolism, growth factor dynamics, and bone healing. Full article

(This article belongs to the Special Issue Advances in Bone Growth, Development and Metabolism)

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16 pages, 791 KiB

Open AccessArticle

Bones or Stones: How Can We Apply Geophysical Techniques in Bone Research?

by Zoltán Szekanecz, Anikó Besnyi, Péter Kónya, Judit Füri, Edit Király, Éva Bertalan, György Falus, Beatrix Udvardi, Viktória Kovács-Kis, László Andrássy, Gyula Maros, Tamás Fancsik, Zsófia Pethő, Izabella Gomez, Ágnes Horváth, Katalin Gulyás, Balázs Juhász, Katalin Hodosi, Zsuzsanna Sándor, Harjit P. Bhattoa and István J. Kovács Show full author list Hide full author list

Int. J. Mol. Sci. 2024, 25(19), 10733; https://doi.org/10.3390/ijms251910733 - 5 Oct 2024

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Abstract

Some studies have used physical techniques for the assessment of bone structure and composition. However, very few studies applied multiple techniques, such as those described below, at the same time. The aim of our study was to determine the chemical and mineralogical/organic composition of bovine tibial bone samples using geophysical/geochemical reference techniques. X-ray diffraction (XRD), thermogravimetry (TG), Fourier-transform infrared spectrometry with attenuated total reflectance accessory (FTIR-ATR), inductively coupled mass spectrometry (ICP-MS) and inductively coupled optical emission spectrometry (ICP-OES) were applied to measure the organic and inorganic composition of 14 bovine bone samples. In addition, peripheral quantitative CT (QCT) was used to assess BMD in these bones. We were able to define the total composition of the studied bone samples. ICP-OES and ICP-MS techniques were used to determine the major and trace element composition. The X-ray analysis could detect inorganic crystalline compounds of bones, such as bioapatite, and its degree of ordering, indicating whether the bones belong to a younger or older individual. The total volatile content of the samples was calculated using TG and resulted in about 35 weight% (wt%). This, together with the 65 wt% total resulting from the chemical analysis (i.e., inorganic components), yielded a total approaching 100 wt%. As a large portion of the volatile content (H₂O, CO₂, etc.) was liberated from the organic components and, subordinately, from bioapatite, it could be concluded that the volatile-to-solid ratio of the examined bone samples was ~35:65. The FTIR-ATR analysis revealed that the organic portion consists of collagens containing amide groups, as their typical bands (OH, CH, CO, NC) were clearly identified in the infrared spectra. Numerous parameters of bone composition correlated with BMD as determined by QCT. In conclusion, we performed a complex evaluation of bovine bones to test multiple geophysical/geochemical techniques in bone research in association with QCT bone densitometry. From a medical point of view, the composition of the studied bones could be reliably examined by these methods. Full article

(This article belongs to the Special Issue Advances in Bone Growth, Development and Metabolism)

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17 pages, 2227 KiB

Open AccessArticle

Influence of Various Strontium Formulations (Ranelate, Citrate, and Chloride) on Bone Mineral Density, Morphology, and Microarchitecture: A Comparative Study in an Ovariectomized Female Mouse Model of Osteoporosis

by Agnieszka Tomczyk-Warunek, Karolina Turżańska, Agnieszka Posturzyńska, Filip Kowal, Tomasz Blicharski, Inés Torné Pano, Anna Winiarska-Mieczan, Anna Nikodem, Sławomir Dresler, Ireneusz Sowa, Magdalena Wójciak and Piotr Dobrowolski

Int. J. Mol. Sci. 2024, 25(7), 4075; https://doi.org/10.3390/ijms25074075 - 6 Apr 2024

Cited by 2 | Viewed by 1912

Abstract

Osteoporosis stands out as a prevalent skeletal ailment, prompting exploration into potential treatments, including dietary strontium ion supplements. This study assessed the efficacy of supplementation of three strontium forms—strontium citrate (SrC), strontium ranelate (SrR), and strontium chloride (SrCl)—for enhancing bone structure in 50 female SWISS mice, aged seven weeks. In total, 40 mice underwent ovariectomy, while 10 underwent sham ovariectomy. Ovariectomized (OVX) mice were randomly assigned to the following groups: OVX (no supplementation), OVX + SrR, OVX + SrC, and OVX + SrCl, at concentrations equivalent to the molar amount of strontium. After 16 weeks, micro-CT examined trabeculae and cortical bones, and whole-bone strontium content was determined. Results confirm strontium administration increased bone tissue mineral density (TMD) and Sr content, with SrC exhibiting the weakest effect. Femur morphometry showed limited Sr impact, especially in the OVX + SrC group. This research highlights strontium’s potential in bone health, emphasizing variations in efficacy among its forms. Full article

(This article belongs to the Special Issue Advances in Bone Growth, Development and Metabolism)

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17 pages, 3116 KiB

Open AccessArticle

(D-Ala²)GIP Inhibits Inflammatory Bone Resorption by Suppressing TNF-α and RANKL Expression and Directly Impeding Osteoclast Formation

by Angyi Lin, Hideki Kitaura, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Jinghan Ma, Jiayi Ren, Mariko Miura, Ziqiu Fan, Kohei Narita and Itaru Mizoguchi

Int. J. Mol. Sci. 2024, 25(5), 2555; https://doi.org/10.3390/ijms25052555 - 22 Feb 2024

Cited by 1 | Viewed by 1851

Abstract

Glucose-insulinotropic polypeptide (GIP) is an incretin hormone that induces insulin secretion and decreases blood glucose levels. In addition, it has been reported to suppress osteoclast formation. Native GIP is rapidly degraded by dipeptidyl peptidase-4 (DPP-4). (D-Ala²)GIP is a newly developed GIP analog that demonstrates enhanced resistance to DPP-4. This study aimed to evaluate the influence of (D-Ala²)GIP on osteoclast formation and bone resorption during lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro. In vivo, mice received supracalvarial injections of LPS with or without (D-Ala²)GIP for 5 days. Osteoclast formation and bone resorption were evaluated, and TNF-α and RANKL expression were measured. In vitro, the influence of (D-Ala²)GIP on RANKL- and TNF-α-induced osteoclastogenesis, LPS-triggered TNF-α expression in macrophages, and RANKL expression in osteoblasts were examined. Compared to the LPS-only group, calvariae co-administered LPS and (D-Ala²)GIP led to less osteoclast formation, lower bone resorption, and decreased TNF-α and RANKL expression. (D-Ala²)GIP inhibited osteoclastogenesis induced by RANKL and TNF-α and downregulated TNF-α expression in macrophages and RANKL expression in osteoblasts in vitro. Furthermore, (D-Ala²)GIP suppressed the MAPK signaling pathway. The results suggest that (D-Ala²)GIP dampened LPS-triggered osteoclast formation and bone resorption in vivo by reducing TNF-α and RANKL expression and directly inhibiting osteoclastogenesis. Full article

(This article belongs to the Special Issue Advances in Bone Growth, Development and Metabolism)

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Review

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17 pages, 609 KiB

Open AccessReview

Circadian Regulation of Bone Remodeling

by Nobuaki Kikyo

Int. J. Mol. Sci. 2024, 25(9), 4717; https://doi.org/10.3390/ijms25094717 - 26 Apr 2024

Cited by 12 | Viewed by 3022

Abstract

Adult bones are continuously remodeled by the balance between bone resorption by osteoclasts and subsequent bone formation by osteoblasts. Many studies have provided molecular evidence that bone remodeling is under the control of circadian rhythms. Circadian fluctuations have been reported in the serum and urine levels of bone turnover markers, such as digested collagen fragments and bone alkaline phosphatase. Additionally, the expressions of over a quarter of all transcripts in bones show circadian rhythmicity, including the genes encoding master transcription factors for osteoblastogenesis and osteoclastogenesis, osteogenic cytokines, and signaling pathway proteins. Serum levels of calcium, phosphate, parathyroid hormone, and calcitonin also display circadian rhythmicity. Finally, osteoblast- and osteoclast-specific knockout mice targeting the core circadian regulator gene Bmal1 show disrupted bone remodeling, although the results have not always been consistent. Despite these studies, however, establishing a direct link between circadian rhythms and bone remodeling in vivo remains a major challenge. It is nearly impossible to repeatedly collect bone materials from human subjects while following circadian changes. In addition, the differences in circadian gene regulation between diurnal humans and nocturnal mice, the main model organism, remain unclear. Filling the knowledge gap in the circadian regulation of bone remodeling could reveal novel regulatory mechanisms underlying many bone disorders including osteoporosis, genetic diseases, and fracture healing. This is also an important question for the basic understanding of how cell differentiation progresses under the influence of cyclically fluctuating environments. Full article

(This article belongs to the Special Issue Advances in Bone Growth, Development and Metabolism)

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30 pages, 1252 KiB

Open AccessReview

Bridging the Gap in Understanding Bone Metastasis: A Multifaceted Perspective

by Basant Elaasser, Nour Arakil and Khalid S. Mohammad

Int. J. Mol. Sci. 2024, 25(5), 2846; https://doi.org/10.3390/ijms25052846 - 29 Feb 2024

Cited by 5 | Viewed by 2961

Abstract

The treatment of patients with advanced cancer poses clinical problems due to the complications that arise as the disease progresses. Bone metastases are a common problem that cancer patients may face, and currently, there are no effective drugs to treat these individuals. Prostate, breast, and lung cancers often spread to the bone, causing significant and disabling health conditions. The bone is a highly active and dynamic tissue and is considered a favorable environment for the growth of cancer. The role of osteoblasts and osteoclasts in the process of bone remodeling and the way in which their interactions change during the progression of metastasis is critical to understanding the pathophysiology of this disease. These interactions create a self-perpetuating loop that stimulates the growth of metastatic cells in the bone. The metabolic reprogramming of both cancer cells and cells in the bone microenvironment has serious implications for the development and progression of metastasis. Insight into the process of bone remodeling and the systemic elements that regulate this process, as well as the cellular changes that occur during the progression of bone metastases, is critical to the discovery of a cure for this disease. It is crucial to explore different therapeutic options that focus specifically on malignancy in the bone microenvironment in order to effectively treat this disease. This review will focus on the bone remodeling process and the effects of metabolic disorders as well as systemic factors like hormones and cytokines on the development of bone metastases. We will also examine the various therapeutic alternatives available today and the upcoming advances in novel treatments. Full article

(This article belongs to the Special Issue Advances in Bone Growth, Development and Metabolism)

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16 pages, 308 KiB

Open AccessReview

Exploring the Interplay between Bone Marrow Stem Cells and Obesity

by Fiorenzo Moscatelli, Antonietta Monda, Giovanni Messina, Elisabetta Picciocchi, Marcellino Monda, Marilena Di Padova, Vincenzo Monda, Antonio Mezzogiorno, Anna Dipace, Pierpaolo Limone, Antonietta Messina and Rita Polito

Int. J. Mol. Sci. 2024, 25(5), 2715; https://doi.org/10.3390/ijms25052715 - 27 Feb 2024

Cited by 1 | Viewed by 2107

Abstract

Obesity, a complex disorder with rising global prevalence, is a chronic, inflammatory, and multifactorial disease and it is characterized by excessive adipose tissue accumulation and associated comorbidities. Adipose tissue (AT) is an extremely diverse organ. The composition, structure, and functionality of AT are significantly influenced by characteristics specific to everyone, in addition to the variability connected to various tissue types and its location-related heterogeneity. Recent investigation has shed light on the intricate relationship between bone marrow stem cells and obesity, revealing potential mechanisms that contribute to the development and consequences of this condition. Mesenchymal stem cells within the bone marrow, known for their multipotent differentiation capabilities, play a pivotal role in adipogenesis, the process of fat cell formation. In the context of obesity, alterations in the bone marrow microenvironment may influence the differentiation of mesenchymal stem cells towards adipocytes, impacting overall fat storage and metabolic balance. Moreover, bone marrow’s role as a crucial component of the immune system adds another layer of complexity to the obesity–bone marrow interplay. This narrative review summarizes the current research findings on the connection between bone marrow stem cells and obesity, highlighting the multifaceted roles of bone marrow in adipogenesis and inflammation. Full article

(This article belongs to the Special Issue Advances in Bone Growth, Development and Metabolism)

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