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Pharmaceuticals
Special Issues
Pharmacological Targets of Bone Homeostasis: Osteoclasts and Osteoblasts
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Pharmacological Targets of Bone Homeostasis: Osteoclasts and Osteoblasts

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 12811

Special Issue Editors

Dr. Jia-Feng Chang

E-Mail Website
Guest Editor
Division of Nephrology, Department of Internal Medicine, Taoyuan Branch of Taipei Veterans General Hospital, Taoyuan 330, Taiwan
Interests: translational medicine in chronic kidney disease, mineral and bone disorders; uremic toxins and vascular calcification; oxidant and inflammatory signaling transduction pathways; novel biomarkers and pharmaceutical targets in prediction models
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ting-Ming Wang

E-Mail Website
Guest Editor
Department of Orthopaedic Surgery, National Taiwan University Hospital, Taipei, Taiwan
Interests: congenital skeletal disorders; orthopedics and novel surgical interventions; gait analysis; therapeutical targets in osteoporosis
Prof. Dr. Kuo-Cheng Lu

E-Mail Website
Guest Editor
Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan
Interests: skeletal properties of renal bone lesions; the effects of uremic-induced bone lesions such as IS/PCS on osteoblasts and osteoclasts; the maturation, differentiation, and function of osteoblasts and osteoclasts

Special Issue Information

Dear Colleagues,

We are pleased to announce a new Special Issue, entitled “Pharmacological Targets of Bone Homeostasis: Osteoclasts and Osteoblasts”, in Pharmaceuticals.

Bone is a highly metabolic organ that is intricately involved in lifelong remodeling to maintain optimal bone architecture and bidirectional signaling transduction between osteoclastic bone resorption and osteoblastic bone formation. In addition to mineral dysregulation, osteoblasts and osteoclasts communicate to influence cellular functions, behavior, proliferation, survival and differentiation through both systemic hormones and local regulation of cytokines/growth factors. Emerging scientific studies have elucidated the pathogenesis peculiarities of bone homeostasis, providing evidence-supported diagnosis and therapeutic recommendations. This Special Issue aims to collect high-quality articles furthering the understanding of molecular mechanisms for multidisciplinary skeletal disorders and effective pharmaceutical targets to provide clinicians with novel evidence-based medicine.

Dr. Jia-Feng Chang
Prof. Dr. Ting-Ming Wang
Prof. Dr. Kuo-Cheng Lu
Guest Editors

Manuscript Submission Information

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. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • translational medicine
  • mineral and bone disorders
  • uremic toxins
  • osteoblast
  • osteoclast
  • pharmaceutical targets
  • congenital skeletal disorders
  • osteoporosis
  • hyperparathyroidism and vitamin D deficiency
  • osteocyte
  • bone remodeling
  • molecular medicine

Published Papers (5 papers)

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Research

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15 pages, 3431 KiB  
Article
Erythromycin Restores Osteoblast Differentiation and Osteogenesis Suppressed by Porphyromonas gingivalis Lipopolysaccharide
by Hikaru Tamura, Tomoki Maekawa, Hisanori Domon, Kridtapat Sirisereephap, Toshihito Isono, Satoru Hirayama, Takumi Hiyoshi, Karin Sasagawa, Fumio Takizawa, Takeyasu Maeda, Yutaka Terao and Koichi Tabeta
Pharmaceuticals 2023, 16(2), 303; https://doi.org/10.3390/ph16020303 - 15 Feb 2023
Cited by 3 | Viewed by 2186
Abstract
The macrolide erythromycin (ERM) inhibits excessive neutrophil accumulation and bone resorption in inflammatory tissues. We previously reported that the expression of developmental endothelial locus-1 (DEL-1), an endogenous anti-inflammatory factor induced by ERM, is involved in ERM action. Furthermore, DEL-1 is involved in the [...] Read more.
The macrolide erythromycin (ERM) inhibits excessive neutrophil accumulation and bone resorption in inflammatory tissues. We previously reported that the expression of developmental endothelial locus-1 (DEL-1), an endogenous anti-inflammatory factor induced by ERM, is involved in ERM action. Furthermore, DEL-1 is involved in the induction of bone regeneration. Therefore, in this study, we investigated whether ERM exerts an osteoblastogenic effect by upregulating DEL-1 under inflammatory conditions. We performed in vitro cell-based mechanistic analyses and used a model of Porphyromonas gingivalis lipopolysaccharide (LPS)-induced periodontitis to evaluate how ERM restores osteoblast activity. In vitro, P. gingivalis LPS stimulation suppressed osteoblast differentiation and bone formation. However, ERM treatment combined with P. gingivalis LPS stimulation upregulated osteoblast differentiation-related factors and Del1, indicating that osteoblast differentiation was restored. Alveolar bone resorption and gene expression were evaluated in a periodontitis model, and the results confirmed that ERM treatment increased DEL-1 expression and suppressed bone loss by increasing the expression of osteoblast-associated factors. In conclusion, ERM restores bone metabolism homeostasis in inflammatory environments possibly via the induction of DEL-1. Full article
(This article belongs to the Special Issue Pharmacological Targets of Bone Homeostasis: Osteoclasts and Osteoblasts)
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12 pages, 1645 KiB  
Article
Denosumab Is Superior to Raloxifene in Lowering Risks of Mortality and Ischemic Stroke in Osteoporotic Women
by Ting-Chun Liu, Chien-Ning Hsu, Wen-Chin Lee, Shih-Wei Wang, Chiang-Chi Huang, Yueh-Ting Lee, Chung-Ming Fu, Jin-Bor Chen and Lung-Chih Li
Pharmaceuticals 2023, 16(2), 222; https://doi.org/10.3390/ph16020222 - 01 Feb 2023
Viewed by 2193
Abstract
Both osteoporosis and cardiovascular disease (CVD) share similar pathways in pathophysiology and are intercorrelated with increased morbidity and mortality in elderly women. Although denosumab and raloxifene are the current guideline-based pharmacological treatments, their impacts on cardiovascular protection are yet to be examined. This [...] Read more.
Both osteoporosis and cardiovascular disease (CVD) share similar pathways in pathophysiology and are intercorrelated with increased morbidity and mortality in elderly women. Although denosumab and raloxifene are the current guideline-based pharmacological treatments, their impacts on cardiovascular protection are yet to be examined. This study aimed to compare mortality rate and cardiovascular events between denosumab and raloxifene in osteoporotic women. Risks of CVD development and all-cause mortality were estimated using Cox proportional hazard regression. A total of 7972 (3986 in each group) women were recruited between January 2003 and December 2018. No significant difference between denosumab and raloxifene was observed in composite CVDs, myocardial infarction, or congestive heart failure. However, comparison of the propensity score matched cohorts revealed that patients with proportion of days covered (PDC) ≥60% had lower incidence of ischemic stroke in the denosumab group than that in the raloxifene group (aHR 0.68; 95% CI 0.47–0.98; p = 0.0399). In addition, all-cause mortality was lower in the denosumab group than in the raloxifene group (aHR 0.59; 95% CI 0.48–0.72; p = 0.001), except in patients aged <65 y/o in this cohort study. We concluded that denosumab is superior to raloxifene in lowering risks of all-cause mortality and certain ischemic strokes in osteoporotic women. Full article
(This article belongs to the Special Issue Pharmacological Targets of Bone Homeostasis: Osteoclasts and Osteoblasts)
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Review

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8 pages, 526 KiB  
Review
Vitamin D and Osteogenesis Imperfecta in Pediatrics
by Francesco Coccia, Angelo Pietrobelli, Thomas Zoller, Alessandra Guzzo, Paolo Cavarzere, Angelo Fassio, Carl-Erik Flodmark, Davide Gatti and Franco Antoniazzi
Pharmaceuticals 2023, 16(5), 690; https://doi.org/10.3390/ph16050690 - 03 May 2023
Cited by 1 | Viewed by 1442
Abstract
Osteogenesis Imperfecta (OI) is a heterogeneous group of inherited skeletal dysplasias characterized by bone fragility. The study of bone metabolism, in these disease, is problematic in terms of clinical and genetic variability. The aims of our study were to evaluate the importance of [...] Read more.
Osteogenesis Imperfecta (OI) is a heterogeneous group of inherited skeletal dysplasias characterized by bone fragility. The study of bone metabolism, in these disease, is problematic in terms of clinical and genetic variability. The aims of our study were to evaluate the importance of Vitamin D levels in OI bone metabolism, reviewing studies performed on this topic and providing advice reflecting our experience using vitamin D supplementation. A comprehensive review on all English-language articles was conducted in order to analyze the influence of vitamin D in OI bone metabolism in pediatric patients. Reviewing the studies, contradictory data were found on the relationship between 25OH vitamin D levels and bone parameters in OI, and in several studies the baseline levels of 25OH D were below the threshold value of 75 nmol/L. In conclusion, according to the literature and to our experience, we highlight the importance of adequate vitamin D supplementation in children with OI. Full article
(This article belongs to the Special Issue Pharmacological Targets of Bone Homeostasis: Osteoclasts and Osteoblasts)
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16 pages, 851 KiB  
Review
The Potential Therapeutic Role of Metformin in Diabetic and Non-Diabetic Bone Impairment
by Wei Mu, Guoqiang Liang, Yue Feng, Yunyun Jiang and Falin Qu
Pharmaceuticals 2022, 15(10), 1274; https://doi.org/10.3390/ph15101274 - 17 Oct 2022
Cited by 3 | Viewed by 2836
Abstract
Metformin is a widely-used anti-diabetic drug in patients with type 2 diabetic mellitus (T2DM) due to its safety and efficacy in clinical. The classic effect of metformin on lowering blood glucose levels is to inhibit liver gluconeogenesis that reduces glucose production as well [...] Read more.
Metformin is a widely-used anti-diabetic drug in patients with type 2 diabetic mellitus (T2DM) due to its safety and efficacy in clinical. The classic effect of metformin on lowering blood glucose levels is to inhibit liver gluconeogenesis that reduces glucose production as well as increases peripheral glucose utilization. However, the factors such as hyperglycemia, insulin deficiency, reduced serum levels of insulin-like growth factor-1 (IGF-1) and osteocalcin, accumulation of advanced glycation end products (AGEs), especially in collagen, microangiopathy, and inflammation reduced bone quality in diabetic patients. However, hyperglycemia, insulin deficiency, reduced levels of insulin-like growth factor-1 (IGF-1) and osteocalcin in serum, accumulation of advanced glycation end products (AGEs) in collagen, microangiopathy, and inflammation, reduce bone quality in diabetic patients. Furthermore, the imbalance of AGE/RAGE results in bone fragility via attenuating osteogenesis. Thus, adequate glycemic control by medical intervention is necessary to prevent bone tissue alterations in diabetic patients. Metformin mainly activates adenosine 5′ -monophosphate-activated protein kinase (AMPK), and inhibits mitochondrial respiratory chain complex I in bone metabolism. In addition, metformin increases the expression of transcription factor runt-related transcription factor2 (RUNX2) and Sirtuin protein to regulate related gene expression in bone formation. Until now, there are a lot of preclinical or clinical findings on the application of metformin to promote bone repair. Taken together, metformin is considered as a potential medication for adjuvant therapy in bone metabolic disorders further to its antidiabetic effect. Taken together, as a conventional hypoglycemia drug with multifaceted effects, metformin has been considered a potential adjuvant drug for the treatment of bone metabolic disorders. Full article
(This article belongs to the Special Issue Pharmacological Targets of Bone Homeostasis: Osteoclasts and Osteoblasts)
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17 pages, 1364 KiB  
Review
Role of Calcimimetics in Treating Bone and Mineral Disorders Related to Chronic Kidney Disease
by Yi-Chou Hou, Cai-Mei Zheng, Hui-Wen Chiu, Wen-Chih Liu, Kuo-Cheng Lu and Chien-Lin Lu
Pharmaceuticals 2022, 15(8), 952; https://doi.org/10.3390/ph15080952 - 31 Jul 2022
Cited by 8 | Viewed by 3246
Abstract
Renal osteodystrophy is common in patients with chronic kidney disease and end-stage renal disease and leads to the risks of fracture and extraosseous vascular calcification. Secondary hyperparathyroidism (SHPT) is characterized by a compensatory increase in parathyroid hormone (PTH) secretion in response to decreased [...] Read more.
Renal osteodystrophy is common in patients with chronic kidney disease and end-stage renal disease and leads to the risks of fracture and extraosseous vascular calcification. Secondary hyperparathyroidism (SHPT) is characterized by a compensatory increase in parathyroid hormone (PTH) secretion in response to decreased renal phosphate excretion, resulting in potentiating bone resorption and decreased bone quantity and quality. Calcium-sensing receptors (CaSRs) are group C G-proteins and negatively regulate the parathyroid glands through (1) increasing CaSR insertion within the plasma membrane, (2) increasing 1,25-dihydroxy vitamin D3 within the kidney and parathyroid glands, (3) inhibiting fibroblast growth factor 23 (FGF23) in osteocytes, and (4) attenuating intestinal calcium absorption through Transient Receptor Potential Vanilloid subfamily member 6 (TRPV6). Calcimimetics (CaMs) decrease PTH concentrations without elevating the serum calcium levels or extraosseous calcification through direct interaction with cell membrane CaSRs. CaMs reduce osteoclast activity by reducing stress-induced oxidative autophagy and improving Wnt-10b release, which promotes the growth of osteoblasts and subsequent mineralization. CaMs also directly promote osteoblast proliferation and survival. Consequently, bone quality may improve due to decreased bone resorption and improved bone formation. CaMs modulate cardiovascular fibrosis, calcification, and renal fibrosis through different mechanisms. Therefore, CaMs assist in treating SHPT. This narrative review focuses on the role of CaMs in renal osteodystrophy, including their mechanisms and clinical efficacy. Full article
(This article belongs to the Special Issue Pharmacological Targets of Bone Homeostasis: Osteoclasts and Osteoblasts)
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