Biology of bone and how it orchestrates the form and function of the skeleton

Abstract

IntroductionThe skeleton's principal role as a structure has predisposed bone to the unfortunate reputation of being an inert and static material. Given bone tissue's ability to adapt its mass and morphology to functional demands, its ability to repair itself without leaving a scar, and its capacity to rapidly mobilize mineral stores on metabolic demand, it is in fact the ultimate "smart" material [43] and a dynamic example of "form follows function" in biological systems [45]. Considering the ever-growing number of patients who suffer from devastating disorders of the skeleton and the ever-increasing opportunities inherent in the post-genomics era to treat diseases and injuries to bone [44], it is critical for both the physician and the scientist to more fully understand the biology of bone and how its ability to form and resorb tissue ultimately orchestrates the structural and metabolic successes of the skeleton. CellsThree distinctly different cell types can be found within bone: the matrix-producing osteoblast, the tissue-resorbing osteoclast, and the osteocyte, which accounts for 90% of all cells in the adult skeleton. Osteocytes can be viewed as highly specialized and fully differentiated osteoblasts; Abstract The principal role of the skeleton is to provide structural support for the body. While the skeleton also serves as the body's mineral reservoir, the mineralized structure is the very basis of posture, opposes muscular contraction resulting in motion, withstands functional load bearing, and protects internal organs. Although the mass and morphology of the skeleton is defined, to some extent, by genetic determinants, it is the tissue's ability to remodel -the local resorption and formation of bone -which is responsible for achieving this intricate balance between competing responsibilities. The aim of this review is to address bone's form-function relationship, beginning with extensive research in the musculoskeletal disciplines, and focusing on several recent cellular and molecular discoveries which help understand the complex interdependence of bone cells, growth factors, physical stimuli, metabolic demands, and structural responsibilities. With a clinical and spine-oriented audience in mind, the principles of bone cell and molecular biology and physiology are presented, and an attempt has been made to incorporate epidemiologic data and therapeutic implications. Bone research remains interdisciplinary by nature, and a deeper understanding of bone biology will ultimately lead to advances in the treatment of diseases and injuries to bone itself.

Chitosan-based scaffolds for bone tissue engineering

“…Osteoid, an unmineralized matrix, is composed mostly (94%) of type I collagen, but also contains signaling proteins, such as growth factors, bone-specific non-collagenous proteins and proteoglycans. 26 During bone formation, the unmineralized matrix is calcified with a non-stoichiometric carbonated apatite. This bone mineral is similar to synthetic and stoichiometric hydroxyapatite and has a plate-like structure (2–6 nm thick, 30–50 nm wide and 60–100 nm long).…”

“…29 When mineralization is complete, calcified bone is composed of approximately 25% organic matrix, 5% water and 70% inorganic mineral. 26 Osteoblasts that become trapped within mineralized matrix further differentiate into osteocytes. Osteocytes are capable of perceiving energy associated with mechanical loading and translating that energy into a biological response involving bone resorption and regeneration, 30 a property known as mechanotransduction.…”

“…31 Finally, osteoclasts, derived from macrophages, are the cells that resorb mineralized bone by forming a tight seal with their apical membrane and secreting lytic enzymes. 26 These bone cells work in concert to maintain the integrity of healthy bone tissue and to regenerate bone that is damaged due to trauma or disease. In the case of critical-sized defects, which are too large to regenerate based on normal remodeling processes, bone grafts are needed to facilitate healing.…”

Cell-based approaches to the engineering of vascularized bone tissue

“…It is characterized by a collagenous extracellular matrix (ECM) that is extensively mineralized with hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ) (15), which is found as plate-like structures 20–80 nm in length (16). Hydroxyapatite contributes to the high density and strength of bone which in turn provides both support and protection to the other tissues and organs of the body.…”

Feeding Blueberry Diets to Young Rats Dose-Dependently Inhibits Bone Resorption through Suppression of RANKL in Stromal Cells

“…Followed by osteoblastic bone formation, osteoclastic bone resorption is essential for maintaining an appropriate, homeostatically controlled amount of bone and shape during the entire early bone developmental period as well as in the adult skeleton [9]. Compared to osteoblasts, which are derived from mesenchymal stem cells (MSCs), osteoclasts are multinucleated cells derived from hematopoietic lineage [10].…”