Osteoimmunology and Bone Biology

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biology biology	3.5	7.4	2012	17.4 Days	CHF 2700
Biomedicines biomedicines	3.9	6.8	2013	17 Days	CHF 2600
Biomolecules biomolecules	4.8	9.2	2011	19.4 Days	CHF 2700
Cells cells	5.2	10.5	2012	16 Days	CHF 2700
International Journal of Molecular Sciences ijms	4.9	9.0	2000	20.5 Days	CHF 2900
Journal of Clinical Medicine jcm	2.9	5.2	2012	17.7 Days	CHF 2600

13 pages, 2027 KB

Open AccessArticle

Cigarette Smoke Exposure Leads to Organic and Mineral Bone Component Changes: The Importance of Rho Kinase Function in These Events

by Alex Ferreira da Silva, Franciele Jesus Lima, Alyne Riani Moreira, Cintia do Nascimento Silva, Ivone Braga de Oliveira, Alexandra Fernandes Callera, Ana Luiza Porfirio, Luan Henrique Vasconcelos Alves, Iolanda de Fátima Lopes Calvo Tibério, Ana Paula Pereira Velosa, Vanda Jorgetti, Walcy Rosolia Teodoro and Fernanda Degobbi Tibério Quirino Dos Santos Lopes

Cells 2025, 14(7), 503; https://doi.org/10.3390/cells14070503 - 28 Mar 2025

Viewed by 569

Abstract

Aberrant Rho-associated kinase function could be associated with increased bone fragility. Since cigarette smoke (CS) exposure promotes the increase in bone fragility due to changes in bone tissue components, this study aimed to investigate how CS exposure could modulate the Rho kinase-associated bone [...] Read more.

Aberrant Rho-associated kinase function could be associated with increased bone fragility. Since cigarette smoke (CS) exposure promotes the increase in bone fragility due to changes in bone tissue components, this study aimed to investigate how CS exposure could modulate the Rho kinase-associated bone structural changes. Mice were assigned to four groups: control; smoke; control with Rho kinase inhibitor administration; and smoke with a Rho kinase inhibitor. Bone samples were obtained to assess bone histomorphometry analysis, type I collagen composition, and MEPE expression in trabeculae. We observed that CS exposure induced decreased trabecular and osteoid thickness. A concomitant increase in the osteoclastic and erosion surfaces and a decrease in the mineralization surface were observed. Additionally, CS exposure decreased the type I collagen and MEPE expression. Rho kinase inhibitor administration recovered the bone mineralization and the collagen type I deposition. Conclusions: CS exposure increases Rho kinase activity in bone cells, leading to structural changes. The administration of a Rho GTPases inhibitor partially reverses these effects, likely due to the recovery in osteoblast activity. Full article

(This article belongs to the Topic Osteoimmunology and Bone Biology)

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13 pages, 2561 KB

Open AccessArticle

Angiotensin II Promotes Osteocyte RANKL Expression via AT1R Activation

by Jiayi Ren, Aseel Marahleh, Jinghan Ma, Fumitoshi Ohori, Takahiro Noguchi, Ziqiu Fan, Jin Hu, Kohei Narita, Angyi Lin and Hideki Kitaura

Biomedicines 2025, 13(2), 426; https://doi.org/10.3390/biomedicines13020426 - 10 Feb 2025

Viewed by 1067

Abstract

Background/Objective: Osteocytes are the most abundant cell type in the skeleton, with key endocrine functions, particularly in regulating osteoblast and osteoclast activity to maintain bone quality. Angiotensin II (Ang II), a critical component of the renin–angiotensin–aldosterone system, is well-known for its role in [...] Read more.

Background/Objective: Osteocytes are the most abundant cell type in the skeleton, with key endocrine functions, particularly in regulating osteoblast and osteoclast activity to maintain bone quality. Angiotensin II (Ang II), a critical component of the renin–angiotensin–aldosterone system, is well-known for its role in vasoconstriction during hypertension. Beyond its cardiovascular functions, Ang II participates in various biological processes, including bone metabolism. While its influence on osteoblast proliferation, differentiation, and osteoclastogenesis has been documented, its effects on osteocytes remain unexplored. This study hypothesized that Ang II enhances the osteoclastogenic activity of osteocytes. Methods: Mouse calvariae were cultured ex vivo in an Ang II-containing medium, analyzed via immunohistochemistry, and evaluated for osteoclastogenic gene expression through real-time PCR. Western blotting was employed to assess protein levels and signaling pathway activation in the MLO-Y4 osteocytic cell line in vitro. Results: Ang II significantly increased the expression of receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). These effects were abrogated by azilsartan, a blocker targeting Ang II type 1 receptors (AT1R). p38 and ERK1/2 in the MAPK pathway were also activated by Ang II. Conclusions: Ang II enhances osteocyte-mediated osteoclastogenesis via AT1R activation, highlighting its potential as a therapeutic target for bone diseases. Full article

(This article belongs to the Topic Osteoimmunology and Bone Biology)

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19 pages, 7655 KB

Open AccessArticle

Proinflammatory Cytokines Enhance the Mineralization, Proliferation, and Metabolic Activity of Primary Human Osteoblast-like Cells

by Juliana Franziska Bousch, Christoph Beyersdorf, Katharina Schultz, Joachim Windolf, Christoph Viktor Suschek and Uwe Maus

Int. J. Mol. Sci. 2024, 25(22), 12358; https://doi.org/10.3390/ijms252212358 - 18 Nov 2024

Cited by 3 | Viewed by 2044

Abstract

Osteoporosis is a progressive metabolic bone disease characterized by decreased bone density and microarchitectural deterioration, leading to an increased risk of fracture, particularly in postmenopausal women and the elderly. Increasing evidence suggests that inflammatory processes play a key role in the pathogenesis of [...] Read more.

Osteoporosis is a progressive metabolic bone disease characterized by decreased bone density and microarchitectural deterioration, leading to an increased risk of fracture, particularly in postmenopausal women and the elderly. Increasing evidence suggests that inflammatory processes play a key role in the pathogenesis of osteoporosis and are strongly associated with the activation of osteoclasts, the cells responsible for bone resorption. In the present study, we investigated, for the first time, the influence of proinflammatory cytokines on the osteogenic differentiation, proliferation, and metabolic activity of primary human osteoblast-like cells (OBs) derived from the femoral heads of elderly patients. We found that all the proinflammatory cytokines, IL-1β, TNF-α, IL-6, and IL-8, enhanced the extracellular matrix mineralization of OBs under differentiation-induced cell culture conditions. In the cases of IL-1β and TNF-α, increased mineralization was correlated with increased osteoblast proliferation. Additionally, IL-1β- and TNF-α-increased osteogenesis was accompanied by a rise in energy metabolism due to improved glycolysis or mitochondrial respiration. In conclusion, we show here, for the first time, that, in contrast to findings obtained with cell lines, mesenchymal stem cells, or animal models, human OBs obtained from patients exhibited significantly enhanced osteogenesis upon exposure to proinflammatory cytokines, probably in part via a mechanism involving enhanced cellular energy metabolism. This study significantly contributes to the field of osteoimmunology by examining a clinically relevant cell model that can help to develop treatments for inflammation-related metabolic bone diseases. Full article

(This article belongs to the Topic Osteoimmunology and Bone Biology)

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15 pages, 3179 KB

Open AccessArticle

CMTM3 Suppresses Proliferation and Osteogenic Transdifferentiation of C2C12 Myoblasts through p53 Upregulation

by Enzhao Shen, Meiyu Piao, Yuankuan Li, Yuecheng Wu, Sihang Li, Sung Ho Lee, Litai Jin and Kwang Youl Lee

Cells 2024, 13(16), 1352; https://doi.org/10.3390/cells13161352 - 14 Aug 2024

Cited by 1 | Viewed by 2427

Abstract

CKLF-like MARVEL transmembrane domain-containing 3 (CMTM3), a member of the CMTM family that is closely related to tumor occurrence and progression, plays crucial roles in the immune system, cardiovascular system, and male reproductive system. Recently, CMTM3 has emerged as a potential target for [...] Read more.

CKLF-like MARVEL transmembrane domain-containing 3 (CMTM3), a member of the CMTM family that is closely related to tumor occurrence and progression, plays crucial roles in the immune system, cardiovascular system, and male reproductive system. Recently, CMTM3 has emerged as a potential target for treating diseases related to bone formation. However, additional studies are needed to understand the mechanisms by which CMTM3 regulates the process of osteogenic differentiation. In this study, we observed a significant downregulation of Cmtm3 expression during the transdifferentiation of C2C12 myoblasts into osteoblasts induced by BMP4. Cmtm3 overexpression suppressed proliferation and osteogenic differentiation in BMP4-induced C2C12 cells, whereas its knockdown conversely facilitated the process. Mechanistically, Cmtm3 overexpression upregulated both the protein and mRNA levels of p53 and p21. Conversely, Cmtm3 knockdown exerted the opposite effects. Additionally, we found that Cmtm3 interacts with p53 and increases protein stability by inhibiting proteasome-mediated ubiquitination and degradation. Notably, Trp53 downregulation abrogated the inhibitory effect of Cmtm3 on BMP4-induced proliferation and osteogenic differentiation of C2C12 myoblasts. Collectively, our findings provide key insights into the role of CMTM3 in regulating myoblast proliferation and transdifferentiation into osteoblasts, highlighting its significance in osteogenesis research. Full article

(This article belongs to the Topic Osteoimmunology and Bone Biology)

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17 pages, 3947 KB

Open AccessArticle

Osteogenic Differentiation of Human Gingival Fibroblasts Inhibits Osteoclast Formation

by Merve Ceylan, Ton Schoenmaker, Jolanda M. A. Hogervorst, Ineke D. C. Jansen, Irene M. Schimmel, Caya M. Prins, Marja L. Laine and Teun J. de Vries

Cells 2024, 13(13), 1090; https://doi.org/10.3390/cells13131090 - 24 Jun 2024

Cited by 5 | Viewed by 5310

Abstract

Gingival fibroblasts (GFs) can differentiate into osteoblast-like cells and induce osteoclast precursors to differentiate into osteoclasts. As it is unclear whether these two processes influence each other, we investigated how osteogenic differentiation of GFs affects their osteoclast-inducing capacity. To establish step-wise mineralization, GFs [...] Read more.

Gingival fibroblasts (GFs) can differentiate into osteoblast-like cells and induce osteoclast precursors to differentiate into osteoclasts. As it is unclear whether these two processes influence each other, we investigated how osteogenic differentiation of GFs affects their osteoclast-inducing capacity. To establish step-wise mineralization, GFs were cultured in four groups for 3 weeks, without or with osteogenic medium for the final 1, 2, or all 3 weeks. The mineralization was assessed by ALP activity, calcium concentration, scanning electron microscopy (SEM), Alizarin Red staining, and quantitative PCR (qPCR). To induce osteoclast differentiation, these cultures were then co-cultured for a further 3 weeks with peripheral blood mononuclear cells (PBMCs) containing osteoclast precursors. Osteoclast formation was assessed at different timepoints with qPCR, enzyme-linked immunosorbent assay (ELISA), TRAcP activity, and staining. ALP activity and calcium concentration increased significantly over time. As confirmed with the Alizarin Red staining, SEM images showed that the mineralization process occurred over time. Osteoclast numbers decreased in the GF cultures that had undergone osteogenesis. TNF-α secretion, a costimulatory molecule for osteoclast differentiation, was highest in the control group. GFs can differentiate into osteoblast-like cells and their degree of differentiation reduces their osteoclast-inducing capacity, indicating that, with appropriate stimulation, GFs could be used in regenerative periodontal treatments. Full article

(This article belongs to the Topic Osteoimmunology and Bone Biology)

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14 pages, 2583 KB

Open AccessArticle

The Expression and Secretion Profile of TRAP5 Isoforms in Gaucher Disease

by Margarita M. Ivanova, Julia Dao, Neala Loynab, Sohailla Noor, Neil Kasaci, Andrew Friedman and Ozlem Goker-Alpan

Cells 2024, 13(8), 716; https://doi.org/10.3390/cells13080716 - 20 Apr 2024

Cited by 2 | Viewed by 2249

Abstract

Background: Gaucher disease (GD) is caused by glucocerebrosidase (GCase) enzyme deficiency, leading to glycosylceramide (Gb-1) and glucosylsphingosine (Lyso-Gb-1) accumulation. The pathological hallmark for GD is an accumulation of large macrophages called Gaucher cells (GCs) in the liver, spleen, and bone marrow, which are [...] Read more.

Background: Gaucher disease (GD) is caused by glucocerebrosidase (GCase) enzyme deficiency, leading to glycosylceramide (Gb-1) and glucosylsphingosine (Lyso-Gb-1) accumulation. The pathological hallmark for GD is an accumulation of large macrophages called Gaucher cells (GCs) in the liver, spleen, and bone marrow, which are associated with chronic organ enlargement, bone manifestations, and inflammation. Tartrate-resistant acid phosphatase type 5 (TRAP5 protein, ACP5 gene) has long been a nonspecific biomarker of macrophage/GCs activation; however, the discovery of two isoforms of TRAP5 has expanded its significance. The discovery of TRAP5′s two isoforms revealed that it is more than just a biomarker of macrophage activity. While TRAP5a is highly expressed in macrophages, TRAP5b is secreted by osteoclasts. Recently, we have shown that the elevation of TRAP5b in plasma is associated with osteoporosis in GD. However, the role of TRAP isoforms in GD and how the accumulation of Gb-1 and Lyso-Gb-1 affects TRAP expression is unknown. Methods: 39 patients with GD were categorized into cohorts based on bone mineral density (BMD). TRAP5a and TRAP5b plasma levels were quantified by ELISA. ACP5 mRNA was estimated using RT-PCR. Results: An increase in TRAP5b was associated with reduced BMD and correlated with Lyso-Gb-1 and immune activator chemokine ligand 18 (CCL18). In contrast, the elevation of TRAP5a correlated with chitotriosidase activity in GD. Lyso-Gb-1 and plasma seemed to influence the expression of ACP5 in macrophages. Conclusions: As an early indicator of BMD alteration, measurement of circulating TRAP5b is a valuable tool for assessing osteopenia–osteoporosis in GD, while TRAP5a serves as a biomarker of macrophage activation in GD. Understanding the distinct expression pattern of TRAP5 isoforms offers valuable insight into both bone disease and the broader implications for immune system activation in GD. Full article

(This article belongs to the Topic Osteoimmunology and Bone Biology)

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19 pages, 4533 KB

Open AccessArticle

Loss of Function of the Retinoblastoma Gene Affects Gap Junctional Intercellular Communication and Cell Fate in Osteoblasts

by Elisha Pendleton, Anthony Ketner, Phil Ransick, Doug Ardekani, Thomas Bodenstine and Nalini Chandar

Biology 2024, 13(1), 39; https://doi.org/10.3390/biology13010039 - 11 Jan 2024

Cited by 2 | Viewed by 2356

Abstract

Loss of function of the Retinoblastoma gene (RB1) due to mutations is commonly seen in human osteosarcomas. One of the Rb1 gene functions is to facilitate cell fate from mesenchymal stem cells to osteoblasts and prevent adipocyte differentiations. In this study, we demonstrate [...] Read more.

Loss of function of the Retinoblastoma gene (RB1) due to mutations is commonly seen in human osteosarcomas. One of the Rb1 gene functions is to facilitate cell fate from mesenchymal stem cells to osteoblasts and prevent adipocyte differentiations. In this study, we demonstrate that a stable reduction of Rb1 expression (RbKD) in murine osteoblasts causes them to express higher levels of PPAR-ɣ and other adipocyte-specific transcription factors while retaining high expression of osteoblast-specific transcription factors, Runx2/Cbfa1 and SP7/Osterix. Inhibition of gap junctional intercellular communication (GJIC) in osteoblasts is another mechanism that causes osteoblasts to transdifferentiate to adipocytes. We found that preosteoblasts exposed to osteoblast differentiating media (DP media) increased GJIC. RbKD cells showed reduced GJIC along with a reduction in expression of Cx43, the protein that mediates GJIC. Other membrane associated adhesion protein Cadherin 11 (Cad11) was also decreased. Since PPAR-ɣ is increased with Rb1 loss, we wondered if the reduction of this transcription factor would reverse the changes observed. Reduction of PPAR-ɣ in control osteoblasts slightly increased bone-specific expression and reduced adipocytic expression as expected along with an increase in Cad11 and Cx43 expression. GJIC remained high and was unaffected by a reduction in PPAR-ɣ in control cells. Knockdown of PPAR-ɣ in RbKD cells reduced adipocyte gene expression, while osteoblast-specific expression showed improvement. Cx43, Cad11 and GJIC remained unaffected by PPAR-ɣ reduction. Our observations suggest that increased PPAR-ɣ that happens with Rb1 loss only affects osteoblast-adipocyte-specific gene expression but does not completely reverse Cx43 gene expression or GJIC. Therefore, these effects may represent independent events triggered by Rb1loss and/or the differentiation process. Full article

(This article belongs to the Topic Osteoimmunology and Bone Biology)

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16 pages, 3194 KB

Open AccessArticle

The Cysteine Protease Legumain Is Upregulated by Vitamin D and Is a Regulator of Vitamin D Metabolism in Mice

by Karl Martin Forbord, Meshail Okla, Ngoc Nguyen Lunde, Tatjana Bosnjak-Olsen, Guro Arnekleiv, Daniel Hesselson, Harald Thidemann Johansen, Jonathan C. Y. Tang, Moustapha Kassem, Rigmor Solberg and Abbas Jafari

Cells 2024, 13(1), 36; https://doi.org/10.3390/cells13010036 - 22 Dec 2023

Cited by 1 | Viewed by 3272

Abstract

Legumain is a lysosomal cysteine protease that has been implicated in an increasing amount of physiological and pathophysiological processes. However, the upstream mechanisms regulating the expression and function of legumain are not well understood. Here, we provide in vitro and in vivo data [...] Read more.

Legumain is a lysosomal cysteine protease that has been implicated in an increasing amount of physiological and pathophysiological processes. However, the upstream mechanisms regulating the expression and function of legumain are not well understood. Here, we provide in vitro and in vivo data showing that vitamin D₃ (VD₃) enhances legumain expression and function. In turn, legumain alters VD₃ bioavailability, possibly through proteolytic cleavage of vitamin D binding protein (VDBP). Active VD₃ (1,25(OH)₂D₃) increased legumain expression, activity, and secretion in osteogenic cultures of human bone marrow stromal cells. Upregulation of legumain was also observed in vivo, evidenced by increased legumain mRNA in the liver and spleen, as well as increased legumain activity in kidneys from wild-type mice treated with 25(OH)D₃ (50 µg/kg, subcutaneously) for 8 days compared to a control. In addition, the serum level of legumain was also increased. We further showed that active legumain cleaved purified VDBP (55 kDa) in vitro, forming a 45 kDa fragment. In vivo, no VDBP cleavage was found in kidneys or liver from legumain-deficient mice (Lgmn^−/−), whereas VDBP was cleaved in wild-type control mice (Lgmn^+/+). Finally, legumain deficiency resulted in increased plasma levels of 25(OH)D₃ and total VD₃ and altered expression of key renal enzymes involved in VD₃ metabolism (CYP24A1 and CYP27B1). In conclusion, a regulatory interplay between VD₃ and legumain is suggested. Full article

(This article belongs to the Topic Osteoimmunology and Bone Biology)

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34 pages, 1972 KB

Open AccessReview

Osteoimmunology of Spondyloarthritis

by Angelo Fassio, Fabiola Atzeni, Maurizio Rossini, Valeria D’Amico, Francesco Cantatore, Maria Sole Chimenti, Chiara Crotti, Bruno Frediani, Andrea Giusti, Giusy Peluso, Guido Rovera, Palma Scolieri, Vincenzo Raimondo, Davide Gatti and on behalf of the Study Group on Osteoporosis and Skeletal Metabolic Diseases of the Italian Society of Rheumatology

Int. J. Mol. Sci. 2023, 24(19), 14924; https://doi.org/10.3390/ijms241914924 - 5 Oct 2023

Cited by 8 | Viewed by 4054

Abstract

The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying [...] Read more.

The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. We summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. Other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA. Full article

(This article belongs to the Topic Osteoimmunology and Bone Biology)

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15 pages, 1622 KB

Open AccessArticle

The Mechanism of Interleukin 33-Induced Stimulation of Interleukin 6 in MLO-Y4 Cells

by Sae Noguchi, Ryota Yamasaki, Yoshie Nagai-Yoshioka, Tsuyoshi Sato, Kayoko Kuroishi, Kaori Gunjigake, Wataru Ariyoshi and Tatsuo Kawamoto

Int. J. Mol. Sci. 2023, 24(19), 14842; https://doi.org/10.3390/ijms241914842 - 2 Oct 2023

Cited by 4 | Viewed by 2546

Abstract

The differentiation and function of osteocytes are controlled by surrounding cells and mechanical stress; however, the detailed mechanisms are unknown. Recent findings suggest that IL-33 is highly expressed in periodontal tissues in orthodontic tooth movement. The present study aimed to elucidate the effect [...] Read more.

The differentiation and function of osteocytes are controlled by surrounding cells and mechanical stress; however, the detailed mechanisms are unknown. Recent findings suggest that IL-33 is highly expressed in periodontal tissues in orthodontic tooth movement. The present study aimed to elucidate the effect of IL-33 on the expression of regulatory factors for bone remodeling and their molecular mechanisms in the osteocyte-like cell line MLO-Y4. MLO-Y4 cells were treated with IL-33, and the activation of intracellular signaling molecules and transcriptional factors was determined using Western blot analysis and chromatin immunoprecipitation assay. IL-33 treatment enhanced the expression of IL-6 in MLO-Y4 cells, which was suppressed by the knockdown of the IL-33 receptor ST2L. Additionally, IL-33 treatment induced activation of NF-κB, JNK/AP-1, and p38 MAPK signaling pathways in MLO-Y4 cells. Moreover, pretreatment with specific inhibitors of NF-κB, p38 MAPK, and JNK/AP-1 attenuated the IL-33-induced expression of IL-6. Furthermore, chromatin immunoprecipitation indicated that IL-33 increased c-Jun recruitment to the IL-6 promoter. Overall, these results suggest that IL-33 induces IL-6 expression and regulates osteocyte function via activation of the NF-κB, JNK/AP-1, and p38 MAPK pathways through interaction with ST2L receptors on the plasma membrane. Full article

(This article belongs to the Topic Osteoimmunology and Bone Biology)

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15 pages, 4928 KB

Open AccessArticle

An Integrative Study on the Inhibition of Bone Loss via Osteo-F Based on Network Pharmacology, Experimental Verification, and Clinical Trials in Postmenopausal Women

by Mi Hye Kim, Minkyung Bok, Hyunjung Lim and Woong Mo Yang

Cells 2023, 12(15), 1992; https://doi.org/10.3390/cells12151992 - 3 Aug 2023

Cited by 6 | Viewed by 2481

Abstract

The inhibition of bone loss remains a challenge for postmenopausal women, considering the fact that only three anabolic treatments for osteoporosis have been approved by the FDA. This study aimed to investigate the osteogenic capacities of Osteo-F, a newly developed herbal formula, upon [...] Read more.

The inhibition of bone loss remains a challenge for postmenopausal women, considering the fact that only three anabolic treatments for osteoporosis have been approved by the FDA. This study aimed to investigate the osteogenic capacities of Osteo-F, a newly developed herbal formula, upon integrating network analysis and pre-clinical studies into clinical trials. The network pharmacology analysis showed that a potential mechanism of Osteo-F is closely related to osteoblast differentiation. Consistent with the predicted mechanism, Osteo-F treatment significantly enhanced bone matrix formation and mineralization with collagen expression in osteoblasts. Simultaneously, secreted bone-forming molecules were upregulated by Osteo-F. After the administration of Osteo-F to osteoporotic mice, the femoral BMD and osteocalcin in the serum and bone tissues were significantly improved. Subsequently, a randomized, double-blinded, placebo-controlled clinical trial showed that 253 mg of Osteo-F supplementation for 24 weeks resulted in significant improvements in the Z-score and serum osteocalcin levels of postmenopausal women compared to the placebo, thus indicating bone anabolic efficacy. In the current study, the bone anabolic effect of Osteo-F was determined by activating the differentiation and mineralization of osteoblasts through integrating experiments based on network analysis into clinical trials, with synchronized, reliable evidence, demonstrating that Osteo-F is a novel bone anabolic treatment in postmenopausal women. Full article

(This article belongs to the Topic Osteoimmunology and Bone Biology)

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13 pages, 1205 KB

Open AccessArticle

In Rats, Whole and Refined Grains Decrease Bone Mineral Density and Content through Modulating Osteoprotegerin and Receptor Activator of Nuclear Factor Kappa B

by Hussein Sakr, Zenat Khired and Marzieh Moghadas

Biomedicines 2023, 11(6), 1686; https://doi.org/10.3390/biomedicines11061686 - 10 Jun 2023

Cited by 2 | Viewed by 2506

Abstract

Wheat is a staple grain in most parts of the world and is also frequently used in livestock feed. The current study looked at the impact of a wheat grain diet on bone turnover markers. Thirty male rats (n = 10) were [...] Read more.

Wheat is a staple grain in most parts of the world and is also frequently used in livestock feed. The current study looked at the impact of a wheat grain diet on bone turnover markers. Thirty male rats (n = 10) were separated into three groups of ten. The rats in Group 1 were fed a chow diet, while the rats in Group 2 were provided whole grains. The rats in Group 3 were fed refined grains. Each rat’s bone mineral content (BMC) and bone mineral density (BMD) were measured after 12 weeks in the tibia of the right hind limb. We also looked at the amounts of bone turnover indicators in the blood. TRAP-5b (Tartrate-resistant acid Phosphatase 5b), NTx (N-telopeptide of type I collagen), DPD (deoxypyridinoline), alkaline phosphatase (ALP), and osteocalcin (OC), as well as the levels of Receptor Activator of Nuclear Factor Kappa B (RANK) and osteoprotegerin (OPG). Rats fed whole and refined grains showed lower BMC and BMD (p < 0.05) than the control group rats. The grain diet resulted in lower OPG, OC, and ALP levels than the chow-fed rats, as well as significantly higher (p < 0.05) levels of RANK, DPD, TRAB 5b, and NTx. In a rat model, an exclusive whole or refined grain diet lowered bone turnover and mass. Full article

(This article belongs to the Topic Osteoimmunology and Bone Biology)

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22 pages, 4494 KB

Open AccessArticle

Anatomical, Histological, and Morphometrical Investigations of the Auditory Ossicles in Chlorocebus aethiops sabaeus from Saint Kitts Island

by Cristian Olimpiu Martonos, Alexandru Ion Gudea, Ioana A. Ratiu, Florin Gheorghe Stan, Pompei Bolfă, William Brady Little and Cristian Constantin Dezdrobitu

Biology 2023, 12(4), 631; https://doi.org/10.3390/biology12040631 - 21 Apr 2023

Cited by 6 | Viewed by 3430

Abstract

Otological studies rely on a lot of data drawn from animal studies. A lot of pathological or evolutionary questions may find answers in studies on primates, providing insights into the morphological, pathological, and physiological aspects of systematic biological studies. Our study on auditory [...] Read more.

Otological studies rely on a lot of data drawn from animal studies. A lot of pathological or evolutionary questions may find answers in studies on primates, providing insights into the morphological, pathological, and physiological aspects of systematic biological studies. Our study on auditory ossicles moves from a pure morphological (macroscopic and microscopic) investigation of auditory ossicles to the morphometrical evaluation of several individuals as well as to some interpretative data regarding some functional aspects drawn from these investigations. Particularities from this perspective blend with metric data and point toward comparative elements that might also serve as an important reference in further morphologic and comparative studies. Full article

(This article belongs to the Topic Osteoimmunology and Bone Biology)

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29 pages, 2505 KB

Open AccessReview

Osteopontin: A Bone-Derived Protein Involved in Rheumatoid Arthritis and Osteoarthritis Immunopathology

by Beatriz Teresita Martín-Márquez, Flavio Sandoval-García, Fernanda Isadora Corona-Meraz, Erika Aurora Martínez-García, Pedro Ernesto Sánchez-Hernández, Mario Salazar-Páramo, Ana Lilia Fletes-Rayas, Daniel González-Inostroz and Monica Vazquez-Del Mercado

Biomolecules 2023, 13(3), 502; https://doi.org/10.3390/biom13030502 - 9 Mar 2023

Cited by 32 | Viewed by 6912

Abstract

Osteopontin (OPN) is a bone-derived phosphoglycoprotein related to physiological and pathological mechanisms that nowadays has gained relevance due to its role in the immune system response to chronic degenerative diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). OPN is an extracellular matrix (ECM) [...] Read more.

Osteopontin (OPN) is a bone-derived phosphoglycoprotein related to physiological and pathological mechanisms that nowadays has gained relevance due to its role in the immune system response to chronic degenerative diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). OPN is an extracellular matrix (ECM) glycoprotein that plays a critical role in bone remodeling. Therefore, it is an effector molecule that promotes joint and cartilage destruction observed in clinical studies, in vitro assays, and animal models of RA and OA. Since OPN undergoes multiple modifications, including posttranslational changes, proteolytic cleavage, and binding to a wide range of receptors, the mechanisms by which it produces its effects, in some cases, remain unclear. Although there is strong evidence that OPN contributes significantly to the immunopathology of RA and OA when considering it as a common denominator molecule, some experimental trial results argue for its protective role in rheumatic diseases. Elucidating in detail OPN involvement in bone and cartilage degeneration is of interest to the field of rheumatology. This review aims to provide evidence of the OPN’s multifaceted role in promoting joint and cartilage destruction and propose it as a common denominator of AR and OA immunopathology. Full article

(This article belongs to the Topic Osteoimmunology and Bone Biology)

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