International Journal of Molecular Sciences

Research

Jump to: Review

20 pages, 5997 KiB

Open AccessArticle

RNA-Binding Proteins as Novel Effectors in Osteoblasts and Osteoclasts: A Systems Biology Approach to Dissect the Transcriptional Landscape

by Anastasia Meshcheryakova, Serhii Bohdan, Philip Zimmermann, Markus Jaritz, Peter Pietschmann and Diana Mechtcheriakova

Int. J. Mol. Sci. 2024, 25(19), 10417; https://doi.org/10.3390/ijms251910417 - 27 Sep 2024

Viewed by 711

Abstract

Bone health is ensured by the coordinated action of two types of cells—the osteoblasts that build up bone structure and the osteoclasts that resorb the bone. The loss of balance in their action results in pathological conditions such as osteoporosis. Central to this [...] Read more.

Bone health is ensured by the coordinated action of two types of cells—the osteoblasts that build up bone structure and the osteoclasts that resorb the bone. The loss of balance in their action results in pathological conditions such as osteoporosis. Central to this study is a class of RNA-binding proteins (RBPs) that regulates the biogenesis of miRNAs. In turn, miRNAs represent a critical level of regulation of gene expression and thus control multiple cellular and biological processes. The impact of miRNAs on the pathobiology of various multifactorial diseases, including osteoporosis, has been demonstrated. However, the role of RBPs in bone remodeling is yet to be elucidated. The aim of this study is to dissect the transcriptional landscape of genes encoding the compendium of 180 RBPs in bone cells. We developed and applied a multi-modular integrative analysis algorithm. The core methodology is gene expression analysis using the GENEVESTIGATOR platform, which is a database and analysis tool for manually curated and publicly available transcriptomic data sets, and gene network reconstruction using the Ingenuity Pathway Analysis platform. In this work, comparative insights into gene expression patterns of RBPs in osteoblasts and osteoclasts were obtained, resulting in the identification of 24 differentially expressed genes. Furthermore, the regulation patterns upon different treatment conditions revealed 20 genes as being significantly up- or down-regulated. Next, novel gene–gene associations were dissected and gene networks were reconstructed. Additively, a set of osteoblast- and osteoclast-specific gene signatures were identified. The consolidation of data and information gained from each individual analytical module allowed nominating novel promising candidate genes encoding RBPs in osteoblasts and osteoclasts and will significantly enhance the understanding of potential regulatory mechanisms directing intracellular processes in the course of (patho)physiological bone turnover. Full article

(This article belongs to the Special Issue Advances in Osteogenesis)

► Show Figures

Graphical abstract

16 pages, 2955 KiB

Open AccessArticle

Selenium Lessens Osteoarthritis by Protecting Articular Chondrocytes from Oxidative Damage through Nrf2 and NF-κB Pathways

by Hsiao-Ling Cheng, Chia-Chi Yen, Li-Wen Huang, Yu-Chen Hu, Tzu-Ching Huang, Bau-Shan Hsieh and Kee-Lung Chang

Int. J. Mol. Sci. 2024, 25(5), 2511; https://doi.org/10.3390/ijms25052511 - 21 Feb 2024

Cited by 3 | Viewed by 1777

Abstract

Osteoarthritis (OA) causes joint pain and disability due to the abnormal production of inflammatory cytokines and reactive oxygen species (ROS) in chondrocytes, leading to cell death and cartilage matrix destruction. Selenium (Se) intake can protect cells against oxidative damage. It is still unknown [...] Read more.

Osteoarthritis (OA) causes joint pain and disability due to the abnormal production of inflammatory cytokines and reactive oxygen species (ROS) in chondrocytes, leading to cell death and cartilage matrix destruction. Selenium (Se) intake can protect cells against oxidative damage. It is still unknown whether Se supplementation is beneficial for OA. This study investigated the effects of Se on sodium iodoacetate (MIA)-imitated OA progress in human chondrocyte cell line (SW1353 cells) and rats. The results showed that 0.3 μM of Se treatment could protect SW1353 cells from MIA-induced damage by the Nrf2 pathway by promoting the gene expression of glutathione-synthesis-related enzymes such as the glutamate–cysteine ligase catalytic subunit, the glutamate–cysteine ligase modifier subunit, and glutathione synthetase. In addition, glutathione, superoxide dismutase, glutathione peroxidase, and glutathione reductase expressions are also elevated to eliminate excessive ROS production. Moreover, Se could downregulate NF-κB, leading to a decrease in cytokines, matrix proteases, and glycosaminoglycans. In the rats, MIA-induced cartilage loss was lessened after 2 weeks of Se supplementation by oral gavage; meanwhile, glutathione synthesis was increased, and the expressions of pro-inflammatory cytokines were decreased. These results suggest that Se intake is beneficial for OA due to its effects of decreasing cartilage loss by enhancing antioxidant capacity and reducing inflammation. Full article

(This article belongs to the Special Issue Advances in Osteogenesis)

► Show Figures

Graphical abstract

16 pages, 5236 KiB

Open AccessArticle

Surface Modification of Polylactic Acid Bioscaffold Fabricated via 3D Printing for Craniofacial Bone Tissue Engineering

by Yao-Chang Liu, Guan-Jie Lo, Victor Bong-Hang Shyu, Chia-Hsuan Tsai, Chih-Hao Chen and Chien-Tzung Chen

Int. J. Mol. Sci. 2023, 24(24), 17410; https://doi.org/10.3390/ijms242417410 - 12 Dec 2023

Cited by 1 | Viewed by 1491

Abstract

Bone tissue engineering is a promising solution for advanced bone defect reconstruction after severe trauma. In bone tissue engineering, scaffolds in three-dimensional (3D) structures are crucial components for cell growth, migration, and infiltration. The three-dimensional printing technique is well suited to manufacturing scaffolds [...] Read more.

Bone tissue engineering is a promising solution for advanced bone defect reconstruction after severe trauma. In bone tissue engineering, scaffolds in three-dimensional (3D) structures are crucial components for cell growth, migration, and infiltration. The three-dimensional printing technique is well suited to manufacturing scaffolds since it can fabricate scaffolds with highly complex designs under good internal structural control. In the current study, the 3D printing technique was utilized to produce polylactic acid (PLA) scaffolds. BMSCs were seeded onto selected scaffolds, either hydrogel-mixed or not, and cultivated in vitro to investigate the osteogenic potential in each group. After osteogenic incubation in vitro, BMSC-seeded scaffolds were implanted onto rat cranium defects, and bone regeneration was observed after 12 weeks. Our results demonstrated that BMSCs were able to seed onto 3D-printed PLA scaffolds under high-resolution observation. Real-time PCR analysis showed their osteogenic ability, which could be further improved after BMSCs were mixed with hydrogel. The in vivo study showed significantly increased bone regeneration when rats’ cranium defects were implanted with a hydrogel-mixed BMSC-seeded scaffold compared to the control and those without cell or hydrogel groups. This study showed that 3D-printed PLA scaffolds are a feasible option for BMSC cultivation and osteogenic differentiation. After mixing with hydrogel, BMSC-seeded 3D-printed scaffolds can facilitate bone regeneration. Full article

(This article belongs to the Special Issue Advances in Osteogenesis)

► Show Figures

Figure 1

12 pages, 3702 KiB

Open AccessArticle

Col1A-2 Mutation in Osteogenesis Imperfecta Mice Contributes to Long Bone Fragility by Modifying Cell-Matrix Organization

by Grégoire André, Antoine Chretien, Antoine Demoulin, Mélanie Beersaerts, Pierre-Louis Docquier and Catherine Behets

Int. J. Mol. Sci. 2023, 24(23), 17010; https://doi.org/10.3390/ijms242317010 - 30 Nov 2023

Cited by 2 | Viewed by 1246

Abstract

Osteogenesis imperfecta (OI) is a rare congenital bone dysplasia generally caused by a mutation of one of the type I collagen genes and characterized by low bone mass, numerous fractures, and bone deformities. The collagen organization and osteocyte lacuna arrangement were investigated in [...] Read more.

Osteogenesis imperfecta (OI) is a rare congenital bone dysplasia generally caused by a mutation of one of the type I collagen genes and characterized by low bone mass, numerous fractures, and bone deformities. The collagen organization and osteocyte lacuna arrangement were investigated in the long bones of 17-week-old wildtype (WT, n = 17) and osteogenesis imperfecta mice (OIM, n = 16) that is a validated model of severe human OI in order to assess their possible role in bone fragility. Fractures were counted after in vivo scanning at weeks 5, 11, and 17. Humerus, femur, and tibia diaphyses from both groups were analyzed ex vivo with pQCT, polarized and ordinary light histology, and Nano-CT. The fractures observed in the OIM were more numerous in the humerus and femur than in the tibia, whereas the quantitative bone parameters were altered in different ways among these bones. Collagen fiber organization appeared disrupted, with a lower birefringence in OIM than WT bones, whereas the osteocyte lacunae were more numerous, more spherical, and not aligned in a lamellar pattern. These modifications, which are typical of immature and less mechanically competent bone, attest to the reciprocal alteration of collagen matrix and osteocyte lacuna organization in the OIM, thereby contributing to bone fragility. Full article

(This article belongs to the Special Issue Advances in Osteogenesis)

► Show Figures

Figure 1

12 pages, 3363 KiB

Open AccessArticle

Deubiquitinase USP17 Regulates Osteoblast Differentiation by Increasing Osterix Protein Stability

by Myeong Ji Kim, Meiyu Piao, Yuankuan Li, Sung Ho Lee and Kwang Youl Lee

Int. J. Mol. Sci. 2023, 24(20), 15257; https://doi.org/10.3390/ijms242015257 - 17 Oct 2023

Cited by 3 | Viewed by 1416

Abstract

Deubiquitinases (DUBs) are essential for bone remodeling by regulating the differentiation of osteoblast and osteoclast. USP17 encodes for a deubiquitinating enzyme, specifically known as ubiquitin-specific protease 17, which plays a critical role in regulating protein stability and cellular signaling pathways. However, the role [...] Read more.

Deubiquitinases (DUBs) are essential for bone remodeling by regulating the differentiation of osteoblast and osteoclast. USP17 encodes for a deubiquitinating enzyme, specifically known as ubiquitin-specific protease 17, which plays a critical role in regulating protein stability and cellular signaling pathways. However, the role of USP17 during osteoblast differentiation has not been elusive. In this study, we initially investigated whether USP17 could regulate the differentiation of osteoblasts. Moreover, USP17 overexpression experiments were conducted to assess the impact on osteoblast differentiation induced by bone morphogenetic protein 4 (BMP4). The positive effect was confirmed through alkaline phosphatase (ALP) expression and activity studies since ALP is a representative marker of osteoblast differentiation. To confirm this effect, Usp17 knockdown was performed, and its impact on BMP4-induced osteoblast differentiation was examined. As expected, knockdown of Usp17 led to the suppression of both ALP expression and activity. Mechanistically, it was observed that USP17 interacted with Osterix (Osx), which is a key transcription factor involved in osteoblast differentiation. Furthermore, overexpression of USP17 led to an increase in Osx protein levels. Thus, to investigate whether this effect was due to the intrinsic function of USP17 in deubiquitination, protein stabilization experiments and ubiquitination analysis were conducted. An increase in Osx protein levels was attributed to an enhancement in protein stabilization via USP17-mediated deubiquitination. In conclusion, USP17 participates in the deubiquitination of Osx, contributing to its protein stabilization, and ultimately promoting the differentiation of osteoblasts. Full article

(This article belongs to the Special Issue Advances in Osteogenesis)

► Show Figures

Figure 1

12 pages, 3137 KiB

Open AccessArticle

BMP-9 Improves the Osteogenic Differentiation Ability over BMP-2 through p53 Signaling In Vitro in Human Periosteum-Derived Cells

by Jin-Ho Park, Eun-Byeol Koh, Young-Jin Seo, Hye-Seong Oh and June-Ho Byun

Int. J. Mol. Sci. 2023, 24(20), 15252; https://doi.org/10.3390/ijms242015252 - 17 Oct 2023

Cited by 5 | Viewed by 1728

Abstract

Bone morphogenetic proteins (BMPs) have tremendous therapeutic potential regarding the treatment of bone and musculoskeletal disorders due to their osteo-inductive ability. More than twenty BMPs have been identified in the human body with various functions, such as embryonic development, skeleton genesis, hematopoiesis, and [...] Read more.

Bone morphogenetic proteins (BMPs) have tremendous therapeutic potential regarding the treatment of bone and musculoskeletal disorders due to their osteo-inductive ability. More than twenty BMPs have been identified in the human body with various functions, such as embryonic development, skeleton genesis, hematopoiesis, and neurogenesis. BMPs can induce the differentiation of MSCs into the osteoblast lineage and promote the proliferation of osteoblasts and chondrocytes. BMP signaling is also involved in tissue remodeling and regeneration processes to maintain homeostasis in adults. In particular, growth factors, such as BMP-2 and BMP-7, have already been approved and are being used as treatments, but it is unclear as to whether they are the most potent BMPs that induce bone formation. According to recent studies, BMP-9 is known to be the most potent inducer of the osteogenic differentiation of mesenchymal stem cells, both in vitro and in vivo. However, its exact role in the skeletal system is still unclear. In addition, research results suggest that the molecular mechanism of BMP-9-mediated bone formation is also different from the previously known BMP family, suggesting that research on signaling pathways related to BMP-9-mediated bone formation is actively being conducted. In this study, we performed a phosphorylation array to investigate the signaling mechanism of BMP-9 compared with BMP-2, another influential bone-forming growth factor, and we compared the downstream signaling system. We present a mechanism for the signal transduction of BMP-9, focusing on the previously known pathway and the p53 factor, which is relatively upregulated compared with BMP-2. Full article

(This article belongs to the Special Issue Advances in Osteogenesis)

► Show Figures

Figure 1

Review

Jump to: Research

12 pages, 721 KiB

Open AccessReview

Effect of Hyperprolactinemia on Bone Metabolism: Focusing on Osteopenia/Osteoporosis

by Soo Jin Yun, Hyunji Sang, So Young Park and Sang Ouk Chin

Int. J. Mol. Sci. 2024, 25(3), 1474; https://doi.org/10.3390/ijms25031474 - 25 Jan 2024

Cited by 3 | Viewed by 3082

Abstract

Prolactin is a hormone secreted from lactotroph cells in the anterior pituitary gland to induce lactation after birth. Hyperprolactinemia unrelated to lactation is a common cause of amenorrhea in women of a childbearing age, and a consequent decrease in the gonadotropin-releasing hormone (GnRH) [...] Read more.

Prolactin is a hormone secreted from lactotroph cells in the anterior pituitary gland to induce lactation after birth. Hyperprolactinemia unrelated to lactation is a common cause of amenorrhea in women of a childbearing age, and a consequent decrease in the gonadotropin-releasing hormone (GnRH) by a high prolactin level can result in decreased bone mineral density. Osteoporosis is a common skeletal disorder characterized by decreased bone mineral density (BMD) and quality, which results in decreased bone strength. In patients with hyperprolactinemia, changes in BMD can be induced indirectly by the inhibition of the GnRH–gonadal axis due to increased prolactin levels or by the direct action of prolactin on osteoblasts and, possibly, osteoclast cells. This review highlights the recent work on bone remodeling and discusses our knowledge of how prolactin modulates these interactions, with a brief literature review on the relationship between prolactin and bone metabolism and suggestions for new possibilities. Full article

(This article belongs to the Special Issue Advances in Osteogenesis)

► Show Figures

Figure 1

22 pages, 1796 KiB

Open AccessReview

Molecular and Cellular Mechanisms of Osteoporosis

by Ivan V. Zhivodernikov, Tatiana V. Kirichenko, Yuliya V. Markina, Anton Y. Postnov and Alexander M. Markin

Int. J. Mol. Sci. 2023, 24(21), 15772; https://doi.org/10.3390/ijms242115772 - 30 Oct 2023

Cited by 21 | Viewed by 7115

Abstract

Osteoporosis is a widespread systemic disease characterized by a decrease in bone mass and an imbalance of the microarchitecture of bone tissue. Experimental and clinical studies devoted to investigating the main pathogenetic mechanisms of osteoporosis revealed the important role of estrogen deficiency, inflammation, [...] Read more.

Osteoporosis is a widespread systemic disease characterized by a decrease in bone mass and an imbalance of the microarchitecture of bone tissue. Experimental and clinical studies devoted to investigating the main pathogenetic mechanisms of osteoporosis revealed the important role of estrogen deficiency, inflammation, oxidative stress, cellular senescence, and epigenetic factors in the development of bone resorption due to osteoclastogenesis, and decreased mineralization of bone tissue and bone formation due to reduced function of osteoblasts caused by apoptosis and age-depended differentiation of osteoblast precursors into adipocytes. The current review was conducted to describe the basic mechanisms of the development of osteoporosis at molecular and cellular levels and to elucidate the most promising therapeutic strategies of pathogenetic therapy of osteoporosis based on articles cited in PubMed up to September 2023. Full article

(This article belongs to the Special Issue Advances in Osteogenesis)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Advances in Osteogenesis

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI