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Biomolecules
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Key Biomolecules in Bone Resorption
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Key Biomolecules in Bone Resorption

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (1 March 2019) | Viewed by 22359

Special Issue Editor

Prof. Dr. L. Shannon Holliday

E-Mail Website
Guest Editor
Department of Orthodontics, and Department of Anatomy & Cell Biology, University of Florida College of Dentistry, Gainesville, FL, USA
Interests: osteoclasts; vacuolar H+-ATPase; actin cytoskeleton; extracellular vesicles; integrins; bone therapeutics

Special Issue Information

Dear Colleagues,

Osteoclasts are specialized cells that differentiate from multipotent hematopoietic precursors. During osteoclastogenesis, they gain the capacity to dissolve bone in a highly-regulated fashion. When osteoclasts contact bone under permissive conditions, they form a unique resorptive apparatus that consists of an actin ring and a ruffled membrane. The actin ring is an exceptionally dynamic, actin based cytoskeletal structure that forces the plasma membrane into the bone, sealing off an extracellular resorption compartment. This compartment is acidified by vacuolar H+-ATPases that pack the ruffled membrane, which is a specialized domain of the plasma membrane bounded by the actin ring. Acidification of the resorption compartment solubilizes bone mineral. Osteoclasts secrete the acid cysteine proteinase cathepsin K, which is active in the acidic environment of the resorption compartment to degrade the organic matrix of the bone. In this Special Issue of Biomolecules, the biomolecules that are vital to activate the formation of the resorption compartment and the key elements of the resorption apparatus will be examined in detail. This will include elements of the activation stage (RANKL/RANK/osteoprotegerin pathway and integrins), the resorption apparatus (actin and its associated proteins and V-ATPase and its accessories) and the signaling that arises from the activation and resorption activity of osteoclasts (extracellular vesicles, ephrins and semaphorins) that help couple bone resorption by osteoclasts with bone formation by osteoblasts. The focus of this Special Issue will be on how these biomolecules are distinctively utilized by osteoclasts to enable these highly specialized cells to accomplish their vital role in bone remodeling.

Prof. Dr. L. Shannon Holliday
Guest Editor

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Keywords

  • osteoclasts
  • bone
  • osteoblasts
  • receptor activator of nuclear factor kappa b (RANK)
  • vacuolar H+-ATPase (V-ATPase)
  • podosome
  • cathepsin K
  • extracellular vesicle
  • exosome
  • integrins
  • cortactin

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Published Papers (4 papers)

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Review

16 pages, 296 KiB  
Review
Advance on Resveratrol Application in Bone Regeneration: Progress and Perspectives for Use in Oral and Maxillofacial Surgery
by Denise Murgia, Rodolfo Mauceri, Giuseppina Campisi and Viviana De Caro
Biomolecules 2019, 9(3), 94; https://doi.org/10.3390/biom9030094 - 8 Mar 2019
Cited by 42 | Viewed by 4783
Abstract
The natural polyphenol Resveratrol (RSV) claims numerous positive effects on health due to the well documented biological effects demonstrating its potential as a disease-preventing agent and as adjuvant for treatment of a wide variety of chronic diseases. Since several studies, both in vitro [...] Read more.
The natural polyphenol Resveratrol (RSV) claims numerous positive effects on health due to the well documented biological effects demonstrating its potential as a disease-preventing agent and as adjuvant for treatment of a wide variety of chronic diseases. Since several studies, both in vitro and in vivo, have highlighted the protective bone aptitude of RSV both as promoter of osteoblasts’ proliferation and antagonist of osteoclasts’ differentiation, they could be interesting in view of applications in the field of dentistry and maxillofacial surgery. This review has brought together experimental findings on the use of RSV in the regeneration of bone tissue comprising also its application associated with scaffolds and non-transfusional hemocomponents. Full article
(This article belongs to the Special Issue Key Biomolecules in Bone Resorption)
15 pages, 2301 KiB  
Review
Specialized Roles for Actin in Osteoclasts: Unanswered Questions and Therapeutic Opportunities
by Guanghong Han, Jian Zuo and Lexie Shannon Holliday
Biomolecules 2019, 9(1), 17; https://doi.org/10.3390/biom9010017 - 9 Jan 2019
Cited by 36 | Viewed by 5496
Abstract
Osteoclasts are cells of the hematopoietic lineage that are specialized to resorb bone. In osteoclasts, the actin cytoskeleton engages in at least two unusual activities that are required for resorption. First, microfilaments form a dynamic and structurally elaborate actin ring. Second, microfilaments bind [...] Read more.
Osteoclasts are cells of the hematopoietic lineage that are specialized to resorb bone. In osteoclasts, the actin cytoskeleton engages in at least two unusual activities that are required for resorption. First, microfilaments form a dynamic and structurally elaborate actin ring. Second, microfilaments bind vacuolar H+-ATPase (V-ATPase) and are involved in forming the V-ATPase-rich ruffled plasma membrane. The current review examines these two specialized functions with emphasis on the identification of new therapeutic opportunities. The actin ring is composed of substructures called podosomes that are interwoven to form a cohesive superstructure. Studies examining the regulation of the formation of actin rings and its constituent proteins are reviewed. Areas where there are gaps in the knowledge are highlighted. Microfilaments directly interact with the V-ATPase through an actin binding site in the B2-subunit of V-ATPase. This binding interaction is required for ruffled membrane formation. Recent studies show that an inhibitor of the interaction blocks bone resorption in pre-clinical animal models, including a model of post-menopausal osteoporosis. Because the unusual actin-based resorption complex is unique to osteoclasts and essential for bone resorption, it is likely that deeper understanding of its underlying mechanisms will lead to new approaches to treat bone disease. Full article
(This article belongs to the Special Issue Key Biomolecules in Bone Resorption)
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16 pages, 613 KiB  
Review
Myosins in Osteoclast Formation and Function
by Beth S. Lee
Biomolecules 2018, 8(4), 157; https://doi.org/10.3390/biom8040157 - 22 Nov 2018
Cited by 25 | Viewed by 5612
Abstract
Skeletal quantity and quality are determined by processes of bone modeling and remodeling, which are undertaken by cells that build and resorb bone as they respond to mechanical, hormonal, and other external and internal signals. As the sole bone resorptive cell type, osteoclasts [...] Read more.
Skeletal quantity and quality are determined by processes of bone modeling and remodeling, which are undertaken by cells that build and resorb bone as they respond to mechanical, hormonal, and other external and internal signals. As the sole bone resorptive cell type, osteoclasts possess a remarkably dynamic actin cytoskeleton that drives their function in this enterprise. Actin rearrangements guide osteoclasts’ capacity for precursor fusion during differentiation, for migration across bone surfaces and sensing of their composition, and for generation of unique actin superstructures required for the resorptive process. In this regard, it is not surprising that myosins, the superfamily of actin-based motor proteins, play key roles in osteoclast physiology. This review briefly summarizes current knowledge of the osteoclast actin cytoskeleton and describes myosins’ roles in osteoclast differentiation, migration, and actin superstructure patterning. Full article
(This article belongs to the Special Issue Key Biomolecules in Bone Resorption)
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6 pages, 429 KiB  
Review
The Role of Calcium in Inflammation-Associated Bone Resorption
by Gordon L. Klein
Biomolecules 2018, 8(3), 69; https://doi.org/10.3390/biom8030069 - 1 Aug 2018
Cited by 30 | Viewed by 5721
Abstract
The aim of this mini-review is to discuss the role of calcium in the process of cytokine-mediated bone resorption in an effort to understand the role circulating calcium may play in the resorption of bone. The liberation of calcium and possibly phosphorus and [...] Read more.
The aim of this mini-review is to discuss the role of calcium in the process of cytokine-mediated bone resorption in an effort to understand the role circulating calcium may play in the resorption of bone. The liberation of calcium and possibly phosphorus and magnesium by bone resorption may sustain and intensify the inflammatory response. We used a burn injury setting in humans and a burn injury model in animals in order to examine the effects on the bone of the systemic inflammatory response and identified the parathyroid calcium-sensing receptor as the mediator of increasing bone resorption, hence higher interleukin (IL)-1 production, and decreasing bone resorption, hence the lowering of circulating ionized calcium concentration. Thus, extracellular calcium, by means of the parathyroid calcium-sensing receptor, is able to modulate inflammation-mediated resorption. Full article
(This article belongs to the Special Issue Key Biomolecules in Bone Resorption)
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