INTRODUCTION
The skeleton represents a unique organ system in the body since, unlike most other organs, the skeletal organ system is composed of a calcified tissue (namely, bone), which consists of about 60% inorganic component (hydroxyapatite), 10% water and 30% organic component (bone matrix proteins) [1-2]. This chemical and biochemical composition of bone renders the skeleton distinct mechanical and biological features which are crucial for its three major functions: providing mechanical support for stature and locomotion, protecting vital organs such as brain and bone marrow, and maintaining mineral homeostasis.
Bone is a dynamic tissue that undergoes constant remodeling (termed bone remodeling) [1,3]. Bone remodeling is a physiological process in which old bone is degraded by osteoclasts, the bone-resorbing cell, and subsequently replaced by new bone formed by osteoblasts, the bone-forming cell [4-7]. The remodeling process plays a crucial role in maintaining a healthy skeleton, which is a prerequisite for a proper execution of the important skeletal functions throughout life [3]. In bone remodeling, differentiation and function of both types of bone cells depend on attachment onto bone [4-7]. Thus, this calcified tissue is not isolated in the body and its maintenance and function requires a close interaction with the cellular components of the body including osteoblasts and osteoclasts.
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While the interaction between bone and bone cells is vital for physiologic functions, aberrant interactions between bone and some other cells have been shown to occur in certain pathological conditions. In particular, a number of cancer cells including those of breast and prostate are capable of interacting with bone and the abnormal interactions are implicated in the metastasis of these tumors to bone [8-9].
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Given that the cell-bone interaction is not only involved in the regulation of physiologic processes but also implicated in the pathogenesis of various disorders including breast and prostate tumor bone metastases, enormous efforts have been undertaken to elucidate the molecular mechanism underlying the cell-bone interaction in the past several decades. Most previous studies have been focused on adhesion molecules belonging to the integrin family since integrins play an important role in cell-extracellular matrix (ECM) protein interaction and numerous bone matrix proteins contain binding motifs for integrins [2,10-11]. As a result, the current notion is that the cell-bone interaction is primarily mediated by integrins. However, emerging evidence does not support this view. Moreover, the chemical and biochemical composition of bone is also inconsistent with this belief.
In this review, I will first provide an overview of the composition of bone as well as the known adhesion molecules. I will then discuss the current understanding of the molecular mechanisms underlying the interaction of bone with osteoclasts, osteoblasts, breast cancer cells and prostate cancer cells. Based on recent findings and the unique chemical and biochemical composition of bone, I will also provide my perspectives that the inorganic, rather than the organic, component of bone is likely to play a predominant role in mediating the cell-bone interaction. I hope that these discussions will facilitate future studies aimed at elucidating the precise molecular basis of the cell-bone interaction, which will not only provide a better understanding of bone biology but, more importantly, may also reveal new therapeutic targets for various bone disorders including osteoporosis and tumor bone metastasis.
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Category: WHY
