Bone functions as an anchorage for muscles enabling movement, and

Bone functions as an anchorage for muscles enabling movement, and as a protective boundary for vital organs such as brain and spinal cord. Its solid characteristics are due to the calcified matrix which is composed of inorganic components of calcium and phosphate, as hydroxyapatite, deposited on organic components, mainly collagen I (Figure 1), and 5% of non-collagenous proteins, such as osteopontin and osteocalcin (Figure 2), etc. The synthesis and calcification of the bone matrix is governed by the osteoblasts (bone-generating cells). The osteoblasts are mostly situated

in the matrix boundaries (Figure 3). The matrix mineralization occurs in matrix vesicles along the collagen fibrils (Figure Inhibitors,research,lifescience,medical 4). We describe how the osteoblasts regulate mineralization of bone matrix. Since the osteoblasts govern the overall process of bone maintenance, their malfunction can cause bone mass depletion, over-production, or production–resorption Inhibitors,research,lifescience,medical imbalance, causing osteoporosis, osteopetrosis, or Paget’s disease of the bone, respectively. Since these pathological conditions are seriously disabling, especially due to their tendency to cause pathological fractures, understanding the cellular regulatory pathways of the osteoblast is crucial for development

of therapeutic modalities for treatment of bone diseases. Figure 1 Microscopic image of immunohistochemical staining for collagen I Inhibitors,research,lifescience,medical (brown color) in cancellous bone sample. Figure 2 Microscopic

image of immunohistochemical staining for osteocalcin (brown color) in cancellous bone sample. Figure 3 Microscopic image Inhibitors,research,lifescience,medical of normal bone sample (HE staining). Figure 4 Microscopic image of Von Kossa staining (calcium bone nodules stained by 5% silver nitrate) adjacent to cultured human osteoblasts. BASIC MULTICELLULAR UNIT (BMU) Bone structural integrity and shape are maintained by removal of old Inhibitors,research,lifescience,medical matrix by osteoclasts and in-situ synthesis of new bone by osteoblasts.1 Resorption and formation are perceived as independent processes but, in reality, they are closely linked within temporary structures called the basic multicellular unit (BMU).2 A fully developed BMU consists of a group of osteoclasts, osteoblasts, blood supply, and connective tissue. As the entire BMU moves forward alongside the bone, osteoclasts resorb bone and die by apoptosis. The average life-span of an osteoclast is about 12 days. The resorbed bone is replaced by osteoblast Metalloexopeptidase cells synthesizing bone matrix. The life-span of osteoblasts varies from a few to about 100 days. The osteoblasts are derived from mesenchymal stem cells (MSCs). Circulating hormones and locally produced cytokines and growth factors modulate the BMS-777607 molecular weight replication and differentiation of osteoclast and osteoblast progenitors. The most important locally produced pro-osteoclastic cytokine is a receptor activator of the nuclear factor ligand (RANKL) or NF-kappaB.

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