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عنوان انگلیسی مقاله:

Visual reporters for study of the osteoblast lineage


سال انتشار : 2016



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مقدمه انگلیسی مقاله:

1. Introduction

Bone is a highly active organ undergoing constant turnover in a coordinated process involving matrix resorption by osteoclasts followed by osteoblast-mediated bone formation. The bone forming cells, the osteoblasts represent 4 to 6% of the cellular content within the bone lineage [1]. These cuboidal-shaped cells cover active bone surfaces. Their major function is to produce new bone by synthesis and assembly of the extracellular matrix. Osteoblasts are thought to be derived from mesenchymal stem/progenitor cells resident near the bone surface that differentiate into the osteogenic lineage, although our understanding of the exact identity, localization and heterogeneity of osteoprogenitors remains incomplete. In contrast, different stages of osteoblast differentiation have been well defined based on cellular properties and gene expression. There are two transcription factors critical for entry into, and differentiation down the osteoblast lineage, Runx2 and osterix (Sp7). Mice with null alleles for both Runx2 and osterix show total absence of bone formation with a completely cartilaginous skeleton [2,3,4]. Osterix is genetically downstream of Runx2, at least under some circumstances, as osterix null cells can express Runx2, but Runx2 null cells never express osterix. Both factors are involved in regulation of important genes in the osteoblast lineage, including genes expressed in pre-osteoblasts such as type I collagen (Cola1, Col1a2), and alkaline phosphatase (ALP, Alpl), as well as markers of more mature osteoblasts bone sialoprotein (BSP, Ibsp), and osteocalcin (Oc, Bglap). During osteoblast differentiation, when Runx2 and Col1a1 are expressed in a pool of progenitors, a proliferation phase is engaged. During this phase, the cells start to acquire ALP activity and are considered pre-osteoblasts. The next stage of differentiation marks the transition to mature osteoblasts. Two steps are essential for the synthesis of the bone matrix: the organic matrix deposition followed by its mineralization. Osteoblasts secrete collagens (mainly collagen type I), non collagenous proteins including Oc, BSP and osteopontin (OPN), and proteoglycans such as decorin and byglycan. Osteoblasts mediate the process of mineralization by producing ALP and secreting matrix vesicles to seed hydroxyapatite crystal formation. Following completion of their matrix forming activity, mature osteoblasts can undergo apoptosis, become embedded in the matrix and differentiate into osteocytes or become quiescent bone lining cells. The understanding of osteoblast biology is critical as numerous skeletal diseases show an impairment of their number or their function resulting in bone defects. The current knowledge of the osteoblast lineage is expanding in the area of identification of the osteoprogenitor cells, along with further defining paracrine and endocrine functions of cells of the osteoblast lineage in vivo. All of these studies require robust methods to identify and target cells of interest.



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کلمات کلیدی:

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