scholarly journals HO-1 in Bone Biology: Potential Therapeutic Strategies for Osteoporosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Xueman Zhou ◽  
Wenxiu Yuan ◽  
Xin Xiong ◽  
Zhenzhen Zhang ◽  
Jiaqi Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Cells ◽  
Current Knowledge ◽  
Bone Microarchitecture ◽  
Osteoporosis Treatment ◽  
Bone Fragility ◽  
Heme Oxygenase 1 ◽  
Bone Homeostasis ◽  
Mass Reduction ◽  
Bone Biology

Osteoporosis is a prevalent bone disorder characterized by bone mass reduction and deterioration of bone microarchitecture leading to bone fragility and fracture risk. In recent decades, knowledge regarding the etiological mechanisms emphasizes that inflammation, oxidative stress and senescence of bone cells contribute to the development of osteoporosis. Studies have demonstrated that heme oxygenase 1 (HO-1), an inducible enzyme catalyzing heme degradation, exhibits anti-inflammatory, anti-oxidative stress and anti-apoptosis properties. Emerging evidence has revealed that HO-1 is critical in the maintenance of bone homeostasis, making HO-1 a potential target for osteoporosis treatment. In this Review, we aim to provide an introduction to current knowledge of HO-1 biology and its regulation, focusing specifically on its roles in bone homeostasis and osteoporosis. We also examine the potential of HO-1-based pharmacological therapeutics for osteoporosis and issues faced during clinical translation.

scholarly journals Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Rinaldo Florencio-Silva ◽  
Gisela Rodrigues da Silva Sasso ◽  
Estela Sasso-Cerri ◽  
Manuel Jesus Simões ◽  
Paulo Sérgio Cerri
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Tissue ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Current Data ◽  
Bone Diseases ◽  
Bone Homeostasis ◽  
Bone Biology ◽  
Structure And Functions

Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

scholarly journals Role of the Complement System in the Response to Orthopedic Biomaterials

2018 ◽  
Vol 19 (11) ◽  
pp. 3367 ◽  
Author(s):  
Yvonne Mödinger ◽  
Graciosa Teixeira ◽  
Cornelia Neidlinger-Wilke ◽  
Anita Ignatius
Keyword(s):  
Complement System ◽  
Bone Cells ◽  
Current Knowledge ◽  
Target Cells ◽  
Host Immune System ◽  
Bone Homeostasis ◽  
Orthopedic Medicine ◽  
Almost All ◽  
The Complement System

Various synthetic biomaterials are used to replace lost or damaged bone tissue that, more or less successfully, osseointegrate into the bone environment. Almost all biomaterials used in orthopedic medicine activate the host-immune system to a certain degree. The complement system, which is a crucial arm of innate immunity, is rapidly activated by an implanted foreign material into the human body, and it is intensely studied regarding blood-contacting medical devices. In contrast, much less is known regarding the role of the complement system in response to implanted bone biomaterials. However, given the increasing knowledge of the complement regulation of bone homeostasis, regeneration, and inflammation, complement involvement in the immune response following biomaterial implantation into bone appears very likely. Moreover, bone cells can produce complement factors and are target cells of activated complement. Therefore, new bone formation or bone resorption around the implant area might be greatly influenced by the complement system. This review aims to summarize the current knowledge on biomaterial-mediated complement activation, with a focus on materials primarily used in orthopedic medicine. In addition, methods to modify the interactions between the complement system and bone biomaterials are discussed, which might favor osseointegration and improve the functionality of the device.

scholarly journals P2Y Receptors in Bone - Anabolic, Catabolic, or Both?

2022 ◽  
Vol 12 ◽  
Author(s):  
Yuhan Zhou ◽  
Hector M. Arredondo ◽  
Ning Wang
Keyword(s):  
Bone Cells ◽  
P2y Receptors ◽  
Extracellular Nucleotides ◽  
Dual Function ◽  
Bone Homeostasis ◽  
Bone Biology ◽  
New Research ◽  
G Protein Coupled ◽  
Targeting Strategy ◽  
Bone Physiology

P2Y receptors, including eight subtypes, are G protein-coupled receptors that can be activated by extracellular nucleotides. Nearly all P2Y receptors are expressed in bone cells, suggesting their involvements in bone physiology and pathology. However, their exact roles in bone homeostasis are not entirely clear. Therefore, this mini review summarizes new research developments regarding individual P2Y receptors and their roles in bone biology, particularly detailing those which execute both anabolic and catabolic functions. This dual function has highlighted the conundrum of pharmacologically targeting these P2Y receptors in bone-wasting diseases. Further research in finding more precise targeting strategy, such as promoting anabolic effects via combining with physical exercise, should be prioritized.

scholarly journals Sex Steroid Regulation of Oxidative Stress in Bone Cells: An In Vitro Study

2021 ◽  
Vol 18 (22) ◽  
pp. 12168
Author(s):  
Valeria Sibilia ◽  
Daniele Bottai ◽  
Roberto Maggi ◽  
Francesca Pagani ◽  
Raffaella Chiaramonte ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Migration ◽  
Protective Effect ◽  
Cell Viability ◽  
Sex Steroids ◽  
Bone Cells ◽  
Free Oxygen Radicals ◽  
Bone Homeostasis ◽  
Transcriptomic Profile

Environmental stimuli, including sex hormones and oxidative stress (OS), affect bone balance, modifying the epigenetic profiles of key osteogenic genes. Nonetheless, the interplay between sex steroids, epigenome and OS has yet be fully elucidated. This paper aims to study in vitro the role of sex steroids in OS-induced alteration in bone cells’ homeostasis, and to assess the possible contribution of epigenetic modifications. Toward this purpose, osteoblast (MC3T3-E1) and osteocyte (MLOY-4) cell lines were exposed to two different sources of free oxygen radicals, i.e., tert-butyl hydroperoxide and dexamethasone, and the protective effect of pre-treatment with androgens and estrogens was evaluated. In particular, we analyzed parameters that reflect bone cell homeostasis such as cell viability, cell migration, transcriptomic profile, transcriptional activity, and epigenetic signature. Our findings indicate that estrogens and androgens counteract OS effects. Using partially overlapping strategies, they reduce OS outcomes regarding cell viability, cell migration, the transcriptomic profile of gene families involved in bone remodeling, and epigenetic profile, i.e., H3K4me3 level. Additionally, we demonstrated that the protective effect of steroids against OS on bone homeostasis is partially mediated by the Akt pathway. Overall, these results suggest that the hormonal milieu may influence the mechanisms of age-related bone disease.

scholarly journals VITAMIN-D DEFICIENCY;

2017 ◽  
Vol 24 (09) ◽  
pp. 1437-1443
Author(s):  
Arif Malik ◽  
Bushra Shaheen ◽  
Muhammad Shahzad Farooq ◽  
Qura-Tul- Ain ◽  
Sulayman Waquar
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Free Radicals ◽  
Bone Cells ◽  
Bone Fractures ◽  
Normal Subjects ◽  
Bone Fragility ◽  
Osteoblastic Activity ◽  
Low Level ◽  
Post Menopausal

Background: Deficiency of vitamin D is characterized by the low bone masswhich leads to the bone fragility and high risk of fractures. Bone fractures causes the formationof free radicals, generated by the tissue damaged. Uncontrolled production of free radicalsaccelerates the oxidative stress and increased the bone remodeling process ultimatelycauses osteoporosis. One of the most damaging effects of free radicals is lipid peroxidation;end product of which is MDA, it also act as major factor in osteoblastic activity. Low level ofantioxidative defense system found in osteoporotic patients due to the deficiency of vitamin D.Many important mineral ions removed from bones and risk of bone fragility increases. Currentstudy is aim to check the antioxidative effect produced from excess reactive oxygen speciescompared with low level of vitamin D which is held responsible for higher or lower activityof bone cells. Study Design: Case Control Study. Setting: Study was conducted at Instituteof Molecular Biology and Biotechnology (IMBB), University of Lahore. Period of Study: Oneyear. Materials and Methods: Blood samples of 272 post-menopausal osteoporotic womenbetween the age 49-57 were collected from Jinnah hospital Lahore. While the samples of 92individuals were served as a control. Concentration of both enzymatic and non-enzymaticantioxidant such as CAT, GSH, SOD, GPx and GR, vitamin A, C and E and levels of MDAwere estimated spectrophotometrically. While the concentration of IL6, AOPPS, AGEs, TNF-α,MMP9, Isoprostanes, LDH, cholesterol, triglycerides, free fatty acids and phospholipid weremeasured by using commercially available Elisa kits. Results: Blood plasma levels of vitaminD were significantly lower in osteoporosis patients than in normal subjects. In addition, levelof stress biomarker such as MDA was found to be higher in patients as compared to control.Due to oxidative stress, level of antioxidants (GSH, CAT, and SOD) was found to be reduced.Blood cells and many other important minerals are also reduces in patient group from theirnormal amount. Conclusion: It concludes that excess production of free radicals over whelmsthe antioxidative system, thus it may leads to osteoporosis. Further more antioxidant speciessubjected to body might protect bone loss and also help in acceleration of healing of fracturedbones.

scholarly journals The Influence of Strontium on Bone Tissue Metabolism and Its Application in Osteoporosis Treatment

2021 ◽  
Vol 22 (12) ◽  
pp. 6564
Author(s):  
Barbara Kołodziejska ◽  
Natalia Stępień ◽  
Joanna Kolmas
Keyword(s):  
Bone Tissue ◽  
Bone Fractures ◽  
Current Knowledge ◽  
Bone Microarchitecture ◽  
Osteoporosis Treatment ◽  
Basic Element ◽  
Calcium Sensing ◽  
Strontium Ions ◽  
Physical And Chemical

Osteoporosis is a chronic disease characterized by low bone mass caused by increased bone turnover and impaired bone microarchitecture. In treatment, we use antiresorptive or anabolic drugs, which usually have a unidirectional effect, i.e., they inhibit the activity of osteoclasts or stimulate the effect of osteoblasts. Strontium ranelate is an anti-osteoporosis drug with a unique mechanism of action (used primarily in postmenopausal women). Unlike other medicines, it has a multidirectional effect on bone tissue, intensifying osteoblastogenesis while inhibiting osteoclastogenesis. It turns out that this effect is demonstrated by strontium ions, an element showing physical and chemical similarity to calcium, the basic element that builds the mineral fraction of bone. As a result, strontium acts through the calcium-sensing receptor (CaSR) receptor in bone tissue cells. In recent years, there has been a significant increase in interest in the introduction of strontium ions in place of calcium ions in ceramics used as bone replacement materials for the treatment of bone fractures and defects caused by osteoporosis. The aim of this study was to summarize current knowledge about the role of strontium in the treatment of osteoporosis, its effects (in various forms), and the ways in which it is administered.

Lactoferrin in Bone Tissue Regeneration

2020 ◽  
Vol 27 (6) ◽  
pp. 838-853 ◽  
Author(s):  
Madalina Icriverzi ◽  
Valentina Dinca ◽  
Magdalena Moisei ◽  
Robert W. Evans ◽  
Mihaela Trif ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Cells ◽  
Bone Diseases ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Bone Tissue Regeneration ◽  
Bone Homeostasis ◽  
Active Compounds

: Among the multiple properties exhibited by lactoferrin (Lf), its involvement in bone regeneration processes is of great interest at the present time. A series of in vitro and in vivo studies have revealed the ability of Lf to promote survival, proliferation and differentiation of osteoblast cells and to inhibit bone resorption mediated by osteoclasts. Although the mechanism underlying the action of Lf in bone cells is still not fully elucidated, it has been shown that its mode of action leading to the survival of osteoblasts is complemented by its mitogenic effect. Activation of several signalling pathways and gene expression, in an LRPdependent or independent manner, has been identified. Unlike the effects on osteoblasts, the action on osteoclasts is different, with Lf leading to a total arrest of osteoclastogenesis. : Due to the positive effect of Lf on osteoblasts, the potential use of Lf alone or in combination with different biologically active compounds in bone tissue regeneration and the treatment of bone diseases is of great interest. Since the bioavailability of Lf in vivo is poor, a nanotechnology- based strategy to improve the biological properties of Lf was developed. The investigated formulations include incorporation of Lf into collagen membranes, gelatin hydrogel, liposomes, loading onto nanofibers, porous microspheres, or coating onto silica/titan based implants. Lf has also been coupled with other biologically active compounds such as biomimetic hydroxyapatite, in order to improve the efficacy of biomaterials used in the regulation of bone homeostasis. : This review aims to provide an up-to-date review of research on the involvement of Lf in bone growth and healing and on its use as a potential therapeutic factor in bone tissue regeneration.

scholarly journals Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models

2021 ◽  
Vol 22 (4) ◽  
pp. 1514 ◽  
Author(s):  
Akihiro Yachie
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Heme Oxygenase ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Pharmacological Intervention ◽  
Heme Oxygenase 1 ◽  
Inflammatory Reactions

Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.

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