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15 pages, 4509 KiB

Open AccessArticle

Altered Osteogenic Differentiation in Mesenchymal Stem Cells Isolated from Compact Bone of Chicken Treated with Varying Doses of Lipopolysaccharides

by Venkata Sesha Reddy Choppa, Guanchen Liu, Yuguo Hou Tompkins and Woo Kyun Kim

Biomolecules 2023, 13(11), 1626; https://doi.org/10.3390/biom13111626 - 7 Nov 2023

Viewed by 1663

Abstract

Persistent inflammation biologically alters signaling molecules and ultimately affects osteogenic differentiation, including in modern-day broilers with unique physiology. Lipopolysaccharides (LPS) are Gram-negative bacterial components that activate cells via transmembrane receptor activation and other molecules. Previous studies have shown several pathways associated with osteogenic [...] Read more.

Persistent inflammation biologically alters signaling molecules and ultimately affects osteogenic differentiation, including in modern-day broilers with unique physiology. Lipopolysaccharides (LPS) are Gram-negative bacterial components that activate cells via transmembrane receptor activation and other molecules. Previous studies have shown several pathways associated with osteogenic inductive ability, but the pathway has yet to be deciphered, and data related to its dose-dependent effect are limited. Primary mesenchymal stem cells (MSCs) were isolated from the bones of day-old broiler chickens, and the current study focused on the dose-dependent variation (3.125 micrograms/mL to 50 micrograms/mL) in osteogenic differentiation and the associated biomarkers in primary MSCs. The doses in this study were determined using a cell viability (MTT) assay. The study revealed that osteogenic differentiation varied with dose, and the cells exposed to higher doses of LPS were viable but lacked differentiating ability. However, this effect became transient with lower doses, and this phenotypic character was observed with differential staining methods like Alizarin Red, Von Kossa, and alkaline phosphatase. The data from this study revealed that LPS at varying doses had a varying effect on osteogenic differentiation via several pathways acting simultaneously during bone development. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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24 pages, 27568 KiB

Open AccessArticle

CC-Chemokine Receptor-2 Expression in Osteoblasts Contributes to Cartilage and Bone Damage during Post-Traumatic Osteoarthritis

by Helen Willcockson, Huseyin Ozkan, José Valdés-Fernández, Liubov Arbeeva, Esra Mucahit, Layla Musawwir, Lola B. Hooper, Froilán Granero-Moltó, Felipe Prósper and Lara Longobardi

Biomolecules 2023, 13(6), 891; https://doi.org/10.3390/biom13060891 - 26 May 2023

Cited by 2 | Viewed by 2809

Abstract

In osteoarthritis (OA), bone changes are radiological hallmarks and are considered important for disease progression. The C-C chemokine receptor-2 (CCR2) has been shown to play an important role in bone physiology. In this study, we investigated whether Ccr2 osteoblast-specific inactivation at different times [...] Read more.

In osteoarthritis (OA), bone changes are radiological hallmarks and are considered important for disease progression. The C-C chemokine receptor-2 (CCR2) has been shown to play an important role in bone physiology. In this study, we investigated whether Ccr2 osteoblast-specific inactivation at different times during post-traumatic OA (PTOA) progression improves joint structures, bone parameters, and pain. We used a tamoxifen-inducible Ccr2 inactivation in Collagen1α-expressing cells to obtain osteoblasts lacking Ccr2 (CCR2-Col1αKO). We stimulated PTOA changes in CCR2-Col1αKO and CCR2+/+ mice using the destabilization of the meniscus model (DMM), inducing recombination before or after DMM (early- vs. late-inactivation). Joint damage was evaluated at two, four, eight, and twelve weeks post-DMM using multiple scores: articular-cartilage structure (ACS), Safranin-O, histomorphometry, osteophyte size/maturity, subchondral bone thickness and synovial hyperplasia. Spontaneous and evoked pain were assessed for up to 20 weeks. We found that early osteoblast-Ccr2 inactivation delayed articular cartilage damage and matrix degeneration compared to CCR2+/+, as well as DMM-induced bone thickness. Osteophyte formation and maturation were only minimally affected. Late Collagen1α-Ccr2 deletion led to less evident improvements. Osteoblast-Ccr2 deletion also improved static measures of pain, while evoked pain did not change. Our study demonstrates that Ccr2 expression in osteoblasts contributes to PTOA disease progression and pain by affecting both cartilage and bone tissues. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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25 pages, 11908 KiB

Open AccessArticle

The Secretome of Parental and Bone Metastatic Breast Cancer Elicits Distinct Effects in Human Osteoclast Activity after Activation of β2 Adrenergic Signaling

by Francisco Conceição, Daniela M. Sousa, Sofia Tojal, Catarina Lourenço, Carina Carvalho-Maia, Helena Estevão-Pereira, João Lobo, Marina Couto, Mette M. Rosenkilde, Carmen Jerónimo and Meriem Lamghari

Biomolecules 2023, 13(4), 622; https://doi.org/10.3390/biom13040622 - 30 Mar 2023

Cited by 4 | Viewed by 2667

Abstract

The sympathetic nervous system (SNS), particularly through the β2 adrenergic receptor (β2-AR), has been linked with breast cancer (BC) and the development of metastatic BC, specifically in the bone. Nevertheless, the potential clinical benefits of exploiting β2-AR antagonists as a treatment for BC [...] Read more.

The sympathetic nervous system (SNS), particularly through the β2 adrenergic receptor (β2-AR), has been linked with breast cancer (BC) and the development of metastatic BC, specifically in the bone. Nevertheless, the potential clinical benefits of exploiting β2-AR antagonists as a treatment for BC and bone loss-associated symptoms remain controversial. In this work, we show that, when compared to control individuals, the epinephrine levels in a cohort of BC patients are augmented in both earlier and late stages of the disease. Furthermore, through a combination of proteomic profiling and functional in vitro studies with human osteoclasts and osteoblasts, we demonstrate that paracrine signaling from parental BC under β2-AR activation causes a robust decrease in human osteoclast differentiation and resorption activity, which is rescued in the presence of human osteoblasts. Conversely, metastatic bone tropic BC does not display this anti-osteoclastogenic effect. In conclusion, the observed changes in the proteomic profile of BC cells under β-AR activation that take place after metastatic dissemination, together with clinical data on epinephrine levels in BC patients, provided new insights on the sympathetic control of breast cancer and its implications on osteoclastic bone resorption. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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15 pages, 4087 KiB

Open AccessArticle

Effect of Hydrogen Oxide-Induced Oxidative Stress on Bone Formation in the Early Embryonic Development Stage of Chicken

by Yuguo Tompkins, Guanchen Liu, Brett Marshall, Milan Kumar Sharma and Woo Kyun Kim

Biomolecules 2023, 13(1), 154; https://doi.org/10.3390/biom13010154 - 12 Jan 2023

Cited by 7 | Viewed by 3011

Abstract

The current study aimed to monitor the impact of H₂O₂-induced oxidative stress on avian bone formation during the early stage of embryonic development. Fertilized Cobb broiler eggs were divided into five treatment groups and micro-injected with varying concentrations of [...] Read more.

The current study aimed to monitor the impact of H₂O₂-induced oxidative stress on avian bone formation during the early stage of embryonic development. Fertilized Cobb broiler eggs were divided into five treatment groups and micro-injected with varying concentrations of H₂O₂, i.e., control (PBS; 0 nM), 10 nM, 30 nM, 100 nM, and 300 nM, on embryonic day 3, with continued incubation thereafter. The treatment concentrations were selected based on the level of lipid peroxidation and the survival rate of embryo. Embryos were collected at 6 h, 24 h, 48 h, and 72 h post-injection. The mRNA expression levels of apoptotic markers, antioxidant enzymes, and early bone formation gene markers were measured. The results showed that the microinjection of H₂O₂ altered the expression pattern of antioxidant enzymes’ mRNA during early embryogenesis and decreased the expression of COL1A2 and COL2A1 at 6 h and 24 h post-injection. Decreased expression of BMP, BGLAP, and RUNX2 was observed 48 h post-injection. Additionally, a shorter embryo length was observed in the 100 nM and 300 nM H₂O₂ treatment groups 72 h post-injection. In conclusion, H₂O₂-induced oxidative stress suppressed the expression of bone formation gene markers, with chronic effects on avian embryonic development. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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18 pages, 4530 KiB

Open AccessArticle

Silencing miR-146a-5p Protects against Injury-Induced Osteoarthritis in Mice

by Haocheng Qin, Cuicui Wang, Yonghua He, Aiwu Lu, Tiandao Li, Bo Zhang and Jie Shen

Biomolecules 2023, 13(1), 123; https://doi.org/10.3390/biom13010123 - 7 Jan 2023

Cited by 11 | Viewed by 2969

Abstract

Osteoarthritis (OA), the most prevalent joint disease and the leading cause of disability, remains an incurable disease largely because the etiology and pathogenesis underlying this degenerative process are poorly understood. Low-grade inflammation within joints is a well-established factor that disturbs joint homeostasis and [...] Read more.

Osteoarthritis (OA), the most prevalent joint disease and the leading cause of disability, remains an incurable disease largely because the etiology and pathogenesis underlying this degenerative process are poorly understood. Low-grade inflammation within joints is a well-established factor that disturbs joint homeostasis and leads to an imbalance between anabolic and catabolic processes in articular cartilage; however, the complexity of the network between inflammatory factors that often involves positive and negative feedback loops makes current anti-cytokine therapy ineffective. MicroRNAs (miRNAs) have emerged as key regulators to control inflammation, and aberrant miRNAs expression has recently been linked to OA pathophysiology. In the present study, we characterized transcriptomic profiles of miRNAs in primary murine articular chondrocytes in response to a proinflammatory cytokine, IL-1β, and identified miR-146a-5p as the most responsive miRNA to IL-1β. miR-146a-5p was also found to be upregulated in human OA cartilage. We further demonstrated that knockdown of miR-146a-5p antagonized IL-1β-mediated inflammatory responses and IL-1β-induced catabolism in vitro, and silencing of miR-146a in chondrocytes ameliorated articular cartilage destruction and reduced OA-evoked pain in an injury-induced murine OA model. Moreover, parallel RNA sequencing revealed that differentially expressed genes in response to IL-1β were enriched in pathways related to inflammatory processes, cartilage matrix homeostasis, and cell metabolism. Bioinformatic analyses of putative miR-146a-5p gene targets and following prediction of protein–protein interactions suggest a functional role of miR-146a-5p in mediating inflammatory processes and regulation of cartilage homeostasis. Our genetic and transcriptomic data define a crucial role of miR-146a-5p in OA pathogenesis and implicate modulation of miR-146a-5p in articular chondrocytes as a potential therapeutic strategy to alleviate OA. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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16 pages, 5401 KiB

Open AccessArticle

Morphometric Changes of Osteocyte Lacunar in Diabetic Pig Mandibular Cancellous Bone

by Sheng Yao, Zhibin Du, Lan Xiao, Fuhua Yan, Saso Ivanovski and Yin Xiao

Biomolecules 2023, 13(1), 49; https://doi.org/10.3390/biom13010049 - 27 Dec 2022

Cited by 7 | Viewed by 2305

Abstract

Osteocytes play an important role in bone metabolism. The interactions of osteocytes with the surrounding microenvironment can alter cellular and lacunar morphological changes. However, objective quantification of osteocyte lacunae is challenging due to their deep location in the bone matrix. This project established [...] Read more.

Osteocytes play an important role in bone metabolism. The interactions of osteocytes with the surrounding microenvironment can alter cellular and lacunar morphological changes. However, objective quantification of osteocyte lacunae is challenging due to their deep location in the bone matrix. This project established a novel method for the analytical study of osteocytes/lacunae, which was then used to evaluate the osteocyte morphological changes in diabetic pig mandibular bone. Eight miniature pigs were sourced, and diabetes was randomly induced in four animals using streptozotocin (STZ) administration. The mandibular tissues were collected and processed. The jawbone density was evaluated with micro-CT. Osteocyte lacunae were effectively acquired and identified using backscattered electron scanning microscopy (BSE). A significantly decreased osteocyte lacunae size was found in the diabetic group. Using the acid etching method, it was demonstrated that the area of osteocyte and lacunae, and the pericellular areas were both significantly reduced in the diabetes group. In conclusion, a standard and relatively reliable method for analyzing osteocyte/lacunae morphological changes under compromised conditions has been successfully established. This method demonstrates that diabetes can significantly decrease osteocyte/lacunae size in a pig’s mandibular cancellous bone. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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22 pages, 2770 KiB

Open AccessArticle

Gabapentin Disrupts Binding of Perlecan to the α₂δ₁ Voltage Sensitive Calcium Channel Subunit and Impairs Skeletal Mechanosensation

by Perla C. Reyes Fernandez, Christian S. Wright, Adrianna N. Masterson, Xin Yi, Tristen V. Tellman, Andrei Bonteanu, Katie Rust, Megan L. Noonan, Kenneth E. White, Karl J. Lewis, Uma Sankar, Julia M. Hum, Gregory Bix, Danielle Wu, Alexander G. Robling, Rajesh Sardar, Mary C. Farach-Carson and William R. Thompson

Biomolecules 2022, 12(12), 1857; https://doi.org/10.3390/biom12121857 - 12 Dec 2022

Cited by 6 | Viewed by 3097

Abstract

Our understanding of how osteocytes, the principal mechanosensors within bone, sense and perceive force remains unclear. Previous work identified “tethering elements” (TEs) spanning the pericellular space of osteocytes and transmitting mechanical information into biochemical signals. While we identified the heparan sulfate proteoglycan perlecan [...] Read more.

Our understanding of how osteocytes, the principal mechanosensors within bone, sense and perceive force remains unclear. Previous work identified “tethering elements” (TEs) spanning the pericellular space of osteocytes and transmitting mechanical information into biochemical signals. While we identified the heparan sulfate proteoglycan perlecan (PLN) as a component of these TEs, PLN must attach to the cell surface to induce biochemical responses. As voltage-sensitive calcium channels (VSCCs) are critical for bone mechanotransduction, we hypothesized that PLN binds the extracellular α₂δ₁ subunit of VSCCs to couple the bone matrix to the osteocyte membrane. Here, we showed co-localization of PLN and α₂δ₁ along osteocyte dendritic processes. Additionally, we quantified the molecular interactions between α₂δ₁ and PLN domains and demonstrated for the first time that α₂δ₁ strongly associates with PLN via its domain III. Furthermore, α₂δ₁ is the binding site for the commonly used pain drug, gabapentin (GBP), which is associated with adverse skeletal effects when used chronically. We found that GBP disrupts PLN::α₂δ₁ binding in vitro, and GBP treatment in vivo results in impaired bone mechanosensation. Our work identified a novel mechanosensory complex within osteocytes composed of PLN and α₂δ₁, necessary for bone force transmission and sensitive to the drug GBP. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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16 pages, 2396 KiB

Open AccessArticle

DAR 16-II Primes Endothelial Cells for Angiogenesis Improving Bone Ingrowth in 3D-Printed BCP Scaffolds and Regeneration of Critically Sized Bone Defects

by Eman Alfayez, Lorenzo Veschini, Monica Dettin, Annj Zamuner, Massimiliano Gaetani, Anna P. Carreca, Stevo Najman, Shahram Ghanaati, Trevor Coward and Lucy Di Silvio

Biomolecules 2022, 12(11), 1619; https://doi.org/10.3390/biom12111619 - 2 Nov 2022

Cited by 2 | Viewed by 2577

Abstract

Bone is a highly vascularized tissue and relies on the angiogenesis and response of cells in the immediate environmental niche at the defect site for regeneration. Hence, the ability to control angiogenesis and cellular responses during osteogenesis has important implications in tissue-engineered strategies. [...] Read more.

Bone is a highly vascularized tissue and relies on the angiogenesis and response of cells in the immediate environmental niche at the defect site for regeneration. Hence, the ability to control angiogenesis and cellular responses during osteogenesis has important implications in tissue-engineered strategies. Self-assembling ionic-complementary peptides have received much interest as they mimic the natural extracellular matrix. Three-dimensional (3D)-printed biphasic calcium phosphate (BCP) scaffolds coated with self-assembling DAR 16-II peptide provide a support template with the ability to recruit and enhance the adhesion of cells. In vitro studies demonstrated prompt the adhesion of both human umbilical vein endothelial cells (HUVEC) and human mesenchymal stem cells (hMSC), favoring endothelial cell activation toward an angiogenic phenotype. The SEM-EDS and protein micro bicinchoninic acid (BCA) assays demonstrated the efficacy of the coating. Whole proteomic analysis of DAR 16-II-treated HUVECs demonstrated the upregulation of proteins involved in cell adhesion (HABP2), migration (AMOTL1), cytoskeletal re-arrangement (SHC1, TMOD2), immuno-modulation (AMBP, MIF), and morphogenesis (COL4A1). In vivo studies using DAR-16-II-coated scaffolds provided an architectural template, promoting cell colonization, osteogenesis, and angiogenesis. In conclusion, DAR 16-II acts as a proactive angiogenic factor when adsorbed onto BCP scaffolds and provides a simple and effective functionalization step to facilitate the translation of tailored 3D-printed BCP scaffolds for clinical applications. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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Review

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16 pages, 1580 KiB

Open AccessReview

Insight into Steroid-Induced ONFH: The Molecular Mechanism and Function of Epigenetic Modification in Mesenchymal Stem Cells

by Chengxiong Huang, Liming Qing, Yu Xiao, Juyu Tang and Panfeng Wu

Biomolecules 2024, 14(1), 4; https://doi.org/10.3390/biom14010004 - 20 Dec 2023

Cited by 5 | Viewed by 2252

Abstract

Osteonecrosis of the femoral head (ONFH) is a common refractory orthopedic disease, which is one of the common causes of hip pain and dysfunction. ONFH has a very high disability rate, which is associated with a heavy burden to patients, families, and society. [...] Read more.

Osteonecrosis of the femoral head (ONFH) is a common refractory orthopedic disease, which is one of the common causes of hip pain and dysfunction. ONFH has a very high disability rate, which is associated with a heavy burden to patients, families, and society. The pathogenesis of ONFH is not completely clear. At present, it is believed that it mainly includes coagulation dysfunction, abnormal lipid metabolism, an imbalance of osteogenic/adipogenic differentiation, and poor vascularization repair. The prevention and treatment of ONFH has always been a great challenge for clinical orthopedic surgeons. However, recent studies have emphasized that the use of mesenchymal stem cells (MSCs) to treat steroid-induced ONFH (SONFH) is a promising therapy. This review focuses on the role and molecular mechanism of epigenetic regulation in the progress of MSCs in the treatment of SONFH, and discusses the significance of the latest research in the treatment of SONFH from the perspective of epigenetics. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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20 pages, 1102 KiB

Open AccessReview

The Past, Present, and Future of Genetically Engineered Mouse Models for Skeletal Biology

by Megan N. Michalski and Bart O. Williams

Biomolecules 2023, 13(9), 1311; https://doi.org/10.3390/biom13091311 - 26 Aug 2023

Cited by 4 | Viewed by 2605

Abstract

The ability to create genetically engineered mouse models (GEMMs) has exponentially increased our understanding of many areas of biology. Musculoskeletal biology is no exception. In this review, we will first discuss the historical development of GEMMs and how these developments have influenced musculoskeletal [...] Read more.

The ability to create genetically engineered mouse models (GEMMs) has exponentially increased our understanding of many areas of biology. Musculoskeletal biology is no exception. In this review, we will first discuss the historical development of GEMMs and how these developments have influenced musculoskeletal disease research. This review will also update our 2008 review that appeared in BONEKey, a journal that is no longer readily available online. We will first review the historical development of GEMMs in general, followed by a particular emphasis on the ability to perform tissue-specific (conditional) knockouts focusing on musculoskeletal tissues. We will then discuss how the development of CRISPR/Cas-based technologies during the last decade has revolutionized the generation of GEMMs. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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16 pages, 2286 KiB

Open AccessEditor’s ChoiceReview

A Review on Pathophysiology, and Molecular Mechanisms of Bacterial Chondronecrosis and Osteomyelitis in Commercial Broilers

by Venkata Sesha Reddy Choppa and Woo Kyun Kim

Biomolecules 2023, 13(7), 1032; https://doi.org/10.3390/biom13071032 - 23 Jun 2023

Cited by 8 | Viewed by 3203

Abstract

Modern day broilers have a great genetic potential to gain heavy bodyweights with a huge metabolic demand prior to their fully mature ages. Moreover, this made the broilers prone to opportunistic pathogens which may enter the locomotory organs under stress causing bacterial chondronecrosis [...] Read more.

Modern day broilers have a great genetic potential to gain heavy bodyweights with a huge metabolic demand prior to their fully mature ages. Moreover, this made the broilers prone to opportunistic pathogens which may enter the locomotory organs under stress causing bacterial chondronecrosis and osteomyelitis (BCO). Such pathogenic colonization is further accelerated by microfractures and clefts that are formed in the bones due to rapid growth rate of the broilers along with ischemia of blood vessels. Furthermore, there are several pathways which alter bone homeostasis like acute phase response, and intrinsic and extrinsic cell death pathways. In contrast, all the affected birds may not exhibit clinical lameness even with the presence of lameness associated factors causing infection. Although Staphylococcus, E. coli, and Enterococcus are considered as common bacterial pathogens involved in BCO, but there exist several other non-culturable bacteria. Any deviation from maintaining a homeostatic environment in the gut might lead to bacterial translocation through blood followed by proliferation of pathogenic bacteria in respective organs including bones. It is important to alleviate dysbiosis of the blood which is analogous to dysbiosis in the gut. This can be achieved by supplementing pro, pre, and synbiotics which helps in providing a eubiotic environment abating the bacterial translocation that was studied to the incidence of BCO. This review focused on potential and novel biomarkers, pathophysiological mechanism, the economic significance of BCO, immune mechanisms, and miscellaneous factors causing BCO. In addition, the role of gut microbiomes along with their diversity and cell culture models from compact bones of chicken in better understanding of BCO were explored. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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14 pages, 977 KiB

Open AccessEditor’s ChoiceReview

An Integrated View of Stressors as Causative Agents in OA Pathogenesis

by Joseph S. Floramo, Vladimir Molchanov, Huadie Liu, Ye Liu, Sonya E. L. Craig and Tao Yang

Biomolecules 2023, 13(5), 721; https://doi.org/10.3390/biom13050721 - 22 Apr 2023

Cited by 4 | Viewed by 4136

Abstract

Cells in the body are exposed to dynamic external and internal environments, many of which cause cell damage. The cell’s response to this damage, broadly called the stress response, is meant to promote survival and repair or remove damage. However, not all damage [...] Read more.

Cells in the body are exposed to dynamic external and internal environments, many of which cause cell damage. The cell’s response to this damage, broadly called the stress response, is meant to promote survival and repair or remove damage. However, not all damage can be repaired, and sometimes, even worse, the stress response can overtax the system itself, further aggravating homeostasis and leading to its loss. Aging phenotypes are considered a manifestation of accumulated cellular damage and defective repair. This is particularly apparent in the primary cell type of the articular joint, the articular chondrocytes. Articular chondrocytes are constantly facing the challenge of stressors, including mechanical overloading, oxidation, DNA damage, proteostatic stress, and metabolic imbalance. The consequence of the accumulation of stress on articular chondrocytes is aberrant mitogenesis and differentiation, defective extracellular matrix production and turnover, cellular senescence, and cell death. The most severe form of stress-induced chondrocyte dysfunction in the joints is osteoarthritis (OA). Here, we summarize studies on the cellular effects of stressors on articular chondrocytes and demonstrate that the molecular effectors of the stress pathways connect to amplify articular joint dysfunction and OA development. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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15 pages, 1420 KiB

Open AccessReview

Cystic Fibrosis Bone Disease: The Interplay between CFTR Dysfunction and Chronic Inflammation

by Óscar Fonseca, Maria Salomé Gomes, Maria Adelina Amorim and Ana Cordeiro Gomes

Biomolecules 2023, 13(3), 425; https://doi.org/10.3390/biom13030425 - 24 Feb 2023

Cited by 6 | Viewed by 3350

Abstract

Cystic fibrosis is a monogenic disease with a multisystemic phenotype, ranging from predisposition to chronic lung infection and inflammation to reduced bone mass. The exact mechanisms unbalancing the maintenance of an optimal bone mass in cystic fibrosis patients remain unknown. Multiple factors may [...] Read more.

Cystic fibrosis is a monogenic disease with a multisystemic phenotype, ranging from predisposition to chronic lung infection and inflammation to reduced bone mass. The exact mechanisms unbalancing the maintenance of an optimal bone mass in cystic fibrosis patients remain unknown. Multiple factors may contribute to severe bone mass reduction that, in turn, have devastating consequences in the patients’ quality of life and longevity. Here, we will review the existing evidence linking the CFTR dysfunction and cell-intrinsic bone defects. Additionally, we will also address how the proinflammatory environment due to CFTR dysfunction in immune cells and chronic infection impairs the maintenance of an adequate bone mass in CF patients. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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16 pages, 1002 KiB

Open AccessReview

Pyroptosis in Periprosthetic Osteolysis

by Jian Yin, Zhaoyang Yin, Peng Lai, Xinhui Liu and Jinzhong Ma

Biomolecules 2022, 12(12), 1733; https://doi.org/10.3390/biom12121733 - 23 Nov 2022

Cited by 15 | Viewed by 3217

Abstract

Periprosthetic osteolysis (PPO) along with aseptic loosening (AL) caused by wear particles after artificial joint replacement is the key factor in surgical failure and subsequent revision surgery, however, the precise molecular mechanism underlying PPO remains unclear. Aseptic inflammation triggered by metal particles, resulting [...] Read more.

Periprosthetic osteolysis (PPO) along with aseptic loosening (AL) caused by wear particles after artificial joint replacement is the key factor in surgical failure and subsequent revision surgery, however, the precise molecular mechanism underlying PPO remains unclear. Aseptic inflammation triggered by metal particles, resulting in the imbalance between bone formation by osteoblasts and bone resorption by osteoclasts may be the decisive factor. Pyroptosis is a new pro-inflammatory pattern of regulated cell death (RCD), mainly mediated by gasdermins (GSDMs) family, among which GSDMD is the best characterized. Recent evidence indicates that activation of NLRP3 inflammasomes and pyroptosis play a pivotal role in the pathological process of PPO. Here, we review the pathological process of PPO, the molecular mechanism of pyroptosis and the interventions to inhibit the inflammation and pyroptosis of different cells during the PPO. Conclusively, this review provides theoretical support for the search for new strategies and new targets for the treatment of PPO by inhibiting pyroptosis and inflammation. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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16 pages, 1567 KiB

Open AccessReview

A Promising Candidate in Tendon Healing Events—PDGF-BB

by Yixuan Chen, Li Jiang, Kexin Lyu, Jingwei Lu, Longhai Long, Xiaoqiang Wang, Tianzhu Liu and Sen Li

Biomolecules 2022, 12(10), 1518; https://doi.org/10.3390/biom12101518 - 20 Oct 2022

Cited by 17 | Viewed by 3806

Abstract

Tendon injuries are one of the most common musculoskeletal disorders for which patients seek medical aid, reducing not only the quality of life of the patient but also imposing a significant economic burden on society. The administration of growth factors at the wound [...] Read more.

Tendon injuries are one of the most common musculoskeletal disorders for which patients seek medical aid, reducing not only the quality of life of the patient but also imposing a significant economic burden on society. The administration of growth factors at the wound site is a feasible solution for enhancing tendon healing. Platelet-derived growth factor-BB (PDGF-BB) has a well-defined safety profile compared to other growth factors and has been approved by the Food and Drug Administration (FDA). The purpose of this review is to summarize the role of PDGF-BB in tendon healing through a comprehensive review of the published literature. Experimental studies suggest that PDGF-BB has a positive effect on tendon healing by enhancing inflammatory responses, speeding up angiogenesis, stimulating tendon cell proliferation, increasing collagen synthesis and increasing the biomechanics of the repaired tendon. PDGF-BB is regarded as a promising candidate in tendon healing. However, in order to realize its full potential, we still need to carefully consider and study key issues such as dose and application time in the future, so as to explore further applications of PDGF-BB in the tendon healing process. Full article

(This article belongs to the Special Issue Recent Advances in Skeletal Development and Diseases)

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