Review
Bone remodeling: Multiple cellular interactions required for coupling of bone formation and resorption

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Abstract

The dynamic nature of the skeleton is achieved by a process called “remodeling” which involves the co-ordinated actions of osteoclasts, osteoblasts, osteocytes within the bone matrix and osteoblast-derived lining cells that cover the surface of bone. Remodeling commences with signals that initiate osteoclast formation followed by osteoclast-mediated bone resorption, a reversal period, and then a long period of bone matrix formation mediated by osteoblasts, followed by mineralisation of the matrix. This review will discuss each of these steps with particular emphasis on the communication pathways between each cell type involved and the roles of ephrins, sclerostin, RANKL and PTHrP.

Section snippets

Remodeling and why it is important

Bone is a dynamic tissue that is constantly formed and resorbed in response to changes in mechanical loading, altered serum calcium levels and in response to a wide range of paracrine and endocrine factors. This dynamic process occurs in both cortical and trabecular (or cancellous) bone allowing a rapid response to changes in circulating calcium levels and, as has become more recently clear, some input into regulating hemopoiesis in adjacent bone marrow [1].

The remodeling cycle and the Basic Multicellular Unit

The dynamic nature of the skeleton is achieved by a process of remodeling; this is the co-ordinated actions of osteoclasts (cells that destroy bone) and osteoblasts (cells that form bone) as well as osteocytes within the bone matrix and osteoblast-derived lining cells that cover the surface of bone. The co-ordinated actions of these cells is described as the “Basic Multicellular Unit”. Within the BMU, cellular activity is matched (or “coupled”), a principle that the amount of bone destroyed by

Initiation of remodeling: control of osteoclast formation and resorption by osteoblasts and osteocytes

Osteoclasts are formed by the attraction of hemopoietic myelomonocytic precursors to the resorption site, followed by their fusion, and attachment of the subsequent multinucleated cell to the bone surface (Fig. 1). The osteoblast lineage plays a critical role in each step of this process.

Osteoclastic control of bone formation

After resorption of a unit of bone by the osteoclast, osteoblasts are then attracted to the surface of bone to begin refilling the pit that remains (Fig. 2). How do the osteoblasts know how much bone is required?

After osteoclasts leave the bone surface, mononuclear cells of unknown origin have been observed on the newly resorbed surface during what is known as a “reversal phase”. These cells have been suggested to be mononuclear phagocytes of hemopoietic origin or osteoblast-lineage cells and

Bone formation controlled within the osteoblast lineage

Osteoid formation by osteoblasts forms one of two types of bone: rapidly deposited woven bone, or more slowly deposited lamellar bone. In part, the type of bone is determined by the manner in which collagen and non-collagenous proteins that make up the osteoid are laid down by the osteoblast, but how this is determined is unknown (for a comprehensive review, see Ref. [87]). Osteoblast differentiation and the deposition of osteoid is controlled, not only by osteoclasts through the mechanisms

Acknowledgements

The authors thank Prof. T.J. Martin, Prof. E. Seeman, and Dr. L.E. Purton for helpful discussions and critical reading of this review.

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