Osteoclasts: more than ‘bone eaters’

Abstract

As the only cells definitively shown to degrade bone, osteoclasts are key mediators of skeletal diseases including osteoporosis. Bone forming osteoblasts, and hematopoietic and immune system cells, each influence osteoclast formation and function, but the reciprocal impact of osteoclasts on these cells is less well appreciated. Here, we highlight functions osteoclasts perform beyond bone resorption. First, we consider how osteoclast signals may contribute to bone formation by osteoblasts and the pathology of bone lesions, such as fibrous dysplasia and giant cell tumors. Second, we review the interaction of osteoclasts with the hematopoietic system, including the stem cell niche and adaptive immune cells. Connections between osteoclasts and other cells in the bone microenvironment are discussed within a clinically relevant framework. Keywordsosteoclast; osteoblast; bone remodeling; osteopetrosis; osteoporosis; PTH Bone remodeling and osteoclasts 101Bone is a composite tissue of protein and mineral, which undergoes continual remodeling to grow, heal damage, and regulate calcium and phosphate metabolism. This remodeling process is executed by the concerted and sequential effort of bone resorbing osteoclasts and bone forming osteoblasts, acting in what has been termed the basic multicellular unit (BMU) ( Figure 1A). Osteocytes, long-lived osteoblast-derived cells that reside within the bone matrix, monitor bone quality and stress, and coordinate remodeling through membrane bound and secreted factors. Skeletal integrity is maintained throughout the lifespan by matching bone formation and resorption, a process referred to as osteoclast:osteoblast 'coupling.' Coupling is thoroughly summarized in recent excellent reviews [1,2] and in Figure 1.Osteoclasts are multinucleated giant cells that differentiate from myeloid precursors under the influence of the cytokines macrophage colony stimulating factor (MCSF) and receptor © 2014 Elsevier Ltd. All rights reserved.Corresponding Author: Antonios O. Aliprantis, M.D., Ph.D., (AALIPRANTIS@PARTNERS.ORG). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript activator of NF-κB ligand (RANKL) supplied by osteoblasts and/or osteocytes ( Figure 1A) [3]. A decoy receptor for RANKL called osteoprotegrin (OPG), which is also made by the osteoblast lineage, tempers osteoclast differentiation [4]. Osteoclasts degrade bone by the polarized secretion of proteolytic enzymes (e.g. cathepsin K) and acid, which hydrolyze and solubilize the organic and inorganic...

Crystallographic and docking (Cathepsins B, K, L and S) studies on bioactive halotelluroxetanes

“…Thus, in order to design a powerful and specific Cathepsin inhibitor, it is of fundamental importance to have detailed knowledge of the features of each sub-site of each Cathepsin [37][38][39]. In addition, it is worth highlighting that this class of enzyme is related to several pathological processes such as osteoporosis (Cathepsin K) [40,41], neurodegenerative disease (Cathepsin D) [42] and metastasis in several types of cancer (Cathepsins B, K, L and S) [43][44][45]. Hence, Cathepsins are promising targets for the treatment of such disorders [46].…”

Osteoclasts promote immune suppressive microenvironment in multiple myeloma: therapeutic implication

“…2 In addition to their major function in bone remodeling, OCs have been recently implicated in multiple complex functions. 3,4 They can regulate the immune system (and this relationship is usually termed as "osteoimmunology"). Specifically, osteoclastic bone resorption is associated with T-cell immune activation in autoimmune disease through crosstalk between OCs and T cells.…”

Gut microbiota induce IGF-1 and promote bone formation and growth

“…The mature skeleton is then remodeled throughout life, with ∼10% of the skeleton being replaced yearly (17). Bone remodeling is a highly regulated process mediated by the activities of bone-resorbing osteoclasts and bone-forming osteoblasts (18). Bone mass is determined by the balance between bone formation and resorption.…”