Osteoblast

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Osteoblast_table_infobox_0

OsteoblastOsteoblast_header_cell_0_0_0
DetailsOsteoblast_header_cell_0_1_0
LocationOsteoblast_header_cell_0_2_0 BoneOsteoblast_cell_0_2_1
FunctionOsteoblast_header_cell_0_3_0 Formation of bone tissueOsteoblast_cell_0_3_1
IdentifiersOsteoblast_header_cell_0_4_0
GreekOsteoblast_header_cell_0_5_0 osteoblastOsteoblast_cell_0_5_1
MeSHOsteoblast_header_cell_0_6_0 Osteoblast_cell_0_6_1
THOsteoblast_header_cell_0_7_0 Osteoblast_cell_0_7_1
FMAOsteoblast_header_cell_0_8_0 Osteoblast_cell_0_8_1

Osteoblasts (from the Greek combining forms for "bone", ὀστέο-, osteo- and βλαστάνω, blastanō "germinate") are cells with a single nucleus that synthesize bone. Osteoblast_sentence_0

However, in the process of bone formation, osteoblasts function in groups of connected cells. Osteoblast_sentence_1

Individual cells cannot make bone. Osteoblast_sentence_2

A group of organized osteoblasts together with the bone made by a unit of cells is usually called the osteon. Osteoblast_sentence_3

Osteoblasts are specialized, terminally differentiated products of mesenchymal stem cells. Osteoblast_sentence_4

They synthesize dense, crosslinked collagen and specialized proteins in much smaller quantities, including osteocalcin and osteopontin, which compose the organic matrix of bone. Osteoblast_sentence_5

In organized groups of connected cells, osteoblasts produce hydroxylapatite - the bone mineral, that is deposited in a highly regulated manner, into the organic matrix forming a strong and dense mineralized tissue - the mineralized matrix. Osteoblast_sentence_6

The mineralized skeleton is the main support for the bodies of air breathing vertebrates. Osteoblast_sentence_7

It is an important store of minerals for physiological homeostasis including both acid-base balance and calcium or phosphate maintenance. Osteoblast_sentence_8

Bone structure Osteoblast_section_0

The skeleton is a large organ that is formed and degraded throughout life in the air-breathing vertebrates. Osteoblast_sentence_9

The skeleton, often referred to as the skeletal system, is important both as a supporting structure and for maintenance of calcium, phosphate, and acid-base status in the whole organism. Osteoblast_sentence_10

The functional part of bone, the bone matrix, is entirely extracellular. Osteoblast_sentence_11

The bone matrix consists of protein and mineral. Osteoblast_sentence_12

The protein forms the organic matrix. Osteoblast_sentence_13

It is synthesized and then the mineral is added. Osteoblast_sentence_14

The vast majority of the organic matrix is collagen, which provides tensile strength. Osteoblast_sentence_15

The matrix is mineralized by deposition of hydroxyapatite (alternative name, hydroxylapatite). Osteoblast_sentence_16

This mineral is hard, and provides compressive strength. Osteoblast_sentence_17

Thus, the collagen and mineral together are a composite material with excellent tensile and compressive strength, which can bend under a strain and recover its shape without damage. Osteoblast_sentence_18

This is called elastic deformation. Osteoblast_sentence_19

Forces that exceed the capacity of bone to behave elastically may cause failure, typically bone fractures. Osteoblast_sentence_20

Bone remodeling Osteoblast_section_1

Bone is a dynamic tissue that is constantly being reshaped by osteoblasts, which produce and secrete matrix proteins and transport mineral into the matrix, and osteoclasts, which break down the tissues. Osteoblast_sentence_21

Osteoblasts Osteoblast_section_2

Osteoblasts are the major cellular component of bone. Osteoblast_sentence_22

Osteoblasts arise from mesenchymal stem cells (MSC). Osteoblast_sentence_23

MSC give rise to osteoblasts, adipocytes, and myocytes among other cell types. Osteoblast_sentence_24

Osteoblast quantity is understood to be inversely proportional to that of marrow adipocytes which comprise marrow adipose tissue (MAT). Osteoblast_sentence_25

Osteoblasts are found in large numbers in the periosteum, the thin connective tissue layer on the outside surface of bones, and in the endosteum. Osteoblast_sentence_26

Normally, almost all of the bone matrix, in the air breathing vertebrates, is mineralized by the osteoblasts. Osteoblast_sentence_27

Before the organic matrix is mineralized, it is called the osteoid. Osteoblast_sentence_28

Osteoblasts buried in the matrix are called osteocytes. Osteoblast_sentence_29

During bone formation, the surface layer of osteoblasts consists of cuboidal cells, called active osteoblasts. Osteoblast_sentence_30

When the bone-forming unit is not actively synthesizing bone, the surface osteoblasts are flattened and are called inactive osteoblasts. Osteoblast_sentence_31

Osteocytes remain alive and are connected by cell processes to a surface layer of osteoblasts. Osteoblast_sentence_32

Osteocytes have important functions in skeletal maintenance. Osteoblast_sentence_33

Osteoclasts Osteoblast_section_3

Osteoclasts are multinucleated cells that derive from hematopoietic progenitors in the bone marrow which also give rise to monocytes in peripheral blood. Osteoblast_sentence_34

Osteoclasts break down bone tissue, and along with osteoblasts and osteocytes form the structural components of bone. Osteoblast_sentence_35

In the hollow within bones are many other cell types of the bone marrow. Osteoblast_sentence_36

Components that are essential for osteoblast bone formation include mesenchymal stem cells (osteoblast precursor) and blood vessels that supply oxygen and nutrients for bone formation. Osteoblast_sentence_37

Bone is a highly vascular tissue, and active formation of blood vessel cells, also from mesenchymal stem cells, is essential to support the metabolic activity of bone. Osteoblast_sentence_38

The balance of bone formation and bone resorption tends to be negative with age, particularly in post-menopausal women, often leading to a loss of bone serious enough to cause fractures, which is called osteoporosis. Osteoblast_sentence_39

Osteogenesis Osteoblast_section_4

Bone is formed by one of two processes: endochondral ossification or intramembranous ossification. Osteoblast_sentence_40

Endochondral ossification is the process of forming bone from cartilage and this is the usual method. Osteoblast_sentence_41

This form of bone development is the more complex form: it follows the formation of a first skeleton of cartilage made by chondrocytes, which is then removed and replaced by bone, made by osteoblasts. Osteoblast_sentence_42

Intramembranous ossification is the direct ossification of mesenchyme as happens during the formation of the membrane bones of the skull and others. Osteoblast_sentence_43

During osteoblast differentiation, the developing progenitor cells express the regulatory transcription factor Cbfa1/Runx2. Osteoblast_sentence_44

A second required transcription factor is Sp7 transcription factor. Osteoblast_sentence_45

Osteochondroprogenitor cells differentiate under the influence of growth factors, although isolated mesenchymal stem cells in tissue culture may also form osteoblasts under permissive conditions that include vitamin C and substrates for alkaline phosphatase, a key enzyme that provides high concentrations of phosphate at the mineral deposition site. Osteoblast_sentence_46

Bone morphogenetic proteins Osteoblast_section_5

Key growth factors in endochondral skeletal differentiation include bone morphogenetic proteins (BMPs) that determine to a major extent where chondrocyte differentiation occurs and where spaces are left between bones. Osteoblast_sentence_47

The system of cartilage replacement by bone has a complex regulatory system. Osteoblast_sentence_48

BMP2 also regulates early skeletal patterning. Osteoblast_sentence_49

transforming growth factor beta (TGF-β), is part of a superfamily of proteins that include BMPs, which possess common signaling elements in the TGF beta signaling pathway. Osteoblast_sentence_50

TGF-β is particularly important in cartilage differentiation, which generally precedes bone formation for endochondral ossification. Osteoblast_sentence_51

An additional family of essential regulatory factors is the fibroblast growth factors (FGFs) that determine where skeletal elements occur in relation to the skin Osteoblast_sentence_52

Steroid and protein hormones Osteoblast_section_6

Many other regulatory systems are involved in the transition of cartilage to bone and in bone maintenance. Osteoblast_sentence_53

A particularly important bone-targeted hormonal regulator is parathyroid hormone (PTH). Osteoblast_sentence_54

Parathyroid hormone is a protein made by the parathyroid gland under the control of serum calcium activity. Osteoblast_sentence_55

PTH also has important systemic functions, including to keep serum calcium concentrations nearly constant regardless of calcium intake. Osteoblast_sentence_56

Increasing dietary calcium results in minor increases in blood calcium. Osteoblast_sentence_57

However, this is not a significant mechanism supporting osteoblast bone formation, except in the condition of low dietary calcium; further, abnormally high dietary calcium raises the risk of serious health consequences not directly related to bone mass including heart attack and stroke. Osteoblast_sentence_58

Intermittent PTH stimulation increases osteoblast activity, although PTH is bifunctional and mediates bone matrix degradation at higher concentrations. Osteoblast_sentence_59

The skeleton is also modified for reproduction and in response to nutritional and other hormone stresses; it responds to steroids, including estrogen and glucocorticoids, which are important in reproduction and energy metabolism regulation. Osteoblast_sentence_60

Bone turnover involves major expenditures of energy for synthesis and degradation, involving many additional signals including pituitary hormones. Osteoblast_sentence_61

Two of these are adrenocorticotropic hormone (ACTH) and follicle stimulating hormone. Osteoblast_sentence_62

The physiological role for responses to these, and several other glycoprotein hormones, is not fully understood, although it is likely that ACTH is bifunctional, like PTH, supporting bone formation with periodic spikes of ACTH, but causing bone destruction in large concentrations. Osteoblast_sentence_63

In mice, mutations that reduce the efficiency of ACTH-induced glucocorticoid production in the adrenals cause the skeleton to become dense (osteosclerotic bone). Osteoblast_sentence_64

Organization and ultrastructure Osteoblast_section_7

In well-preserved bone studied at high magnification via electron microscopy, individual osteoblasts are shown to be connected by tight junctions, which prevent extracellular fluid passage and thus create a bone compartment separate from the general extracellular fluid. Osteoblast_sentence_65

The osteoblasts are also connected by gap junctions, small pores that connect osteoblasts, allowing the cells in one cohort to function as a unit. Osteoblast_sentence_66

The gap junctions also connect deeper layers of cells to the surface layer (osteocytes when surrounded by bone). Osteoblast_sentence_67

This was demonstrated directly by injecting low molecular weight fluorescent dyes into osteoblasts and showing that the dye diffused to surrounding and deeper cells in the bone-forming unit. Osteoblast_sentence_68

Bone is composed of many of these units, which are separated by impermeable zones with no cellular connections, called cement lines. Osteoblast_sentence_69

Collagen and accessory proteins Osteoblast_section_8

Almost all of the organic (non-mineral) component of bone is dense collagen type I, which forms dense crosslinked ropes that give bone its tensile strength. Osteoblast_sentence_70

By mechanisms still unclear, osteoblasts secrete layers of oriented collagen, with the layers parallel to the long axis of the bone alternating with layers at right angles to the long axis of the bone every few micrometers. Osteoblast_sentence_71

Defects in collagen type I cause the commonest inherited disorder of bone, called osteogenesis imperfecta. Osteoblast_sentence_72

Minor, but important, amounts of small proteins, including osteocalcin and osteopontin, are secreted in bone's organic matrix. Osteoblast_sentence_73

Osteocalcin is not expressed at significant concentrations except in bone, and thus osteocalcin is a specific marker for bone matrix synthesis. Osteoblast_sentence_74

These proteins link organic and mineral component of bone matrix. Osteoblast_sentence_75

The proteins are necessary for maximal matrix strength due to their intermediate localization between mineral and collagen. Osteoblast_sentence_76

However, in mice where expression of osteocalcin or osteopontin was eliminated by targeted disruption of the respective genes (knockout mice), accumulation of mineral was not notably affected, indicating that organization of matrix is not significantly related to mineral transport. Osteoblast_sentence_77

Bone versus cartilage Osteoblast_section_9

The primitive skeleton is cartilage, a solid avascular (without blood vessels) tissue in which individual cartilage-matrix secreting cells, or chondrocytes, occur. Osteoblast_sentence_78

Chondrocytes do not have intercellular connections and are not coordinated in units. Osteoblast_sentence_79

Cartilage is composed of a network of collagen type II held in tension by water-absorbing proteins, hydrophilic proteoglycans. Osteoblast_sentence_80

This is the adult skeleton in cartilaginous fishes such as sharks. Osteoblast_sentence_81

It develops as the initial skeleton in more advanced classes of animals. Osteoblast_sentence_82

In air-breathing vertebrates, cartilage is replaced by cellular bone. Osteoblast_sentence_83

A transitional tissue is mineralized cartilage. Osteoblast_sentence_84

Cartilage mineralizes by massive expression of phosphate-producing enzymes, which cause high local concentrations of calcium and phosphate that precipitate. Osteoblast_sentence_85

This mineralized cartilage is not dense or strong. Osteoblast_sentence_86

In the air breathing vertebrates it is used as a scaffold for formation of cellular bone made by osteoblasts, and then it is removed by osteoclasts, which specialize in degrading mineralized tissue. Osteoblast_sentence_87

Osteoblasts produce an advanced type of bone matrix consisting of dense, irregular crystals of hydroxyapatite, packed around the collagen ropes. Osteoblast_sentence_88

This is a strong composite material that allows the skeleton to be shaped mainly as hollow tubes. Osteoblast_sentence_89

Reducing the long bones to tubes reduces weight while maintaining strength. Osteoblast_sentence_90

Mineralization of bone Osteoblast_section_10

The mechanisms of mineralization are not fully understood. Osteoblast_sentence_91

Fluorescent, low-molecular weight compounds such as tetracycline or calcein bind strongly to bone mineral, when administered for short periods. Osteoblast_sentence_92

They then accumulate in narrow bands in the new bone. Osteoblast_sentence_93

These bands run across the contiguous group of bone-forming osteoblasts. Osteoblast_sentence_94

They occur at a narrow (sub-micrometer) mineralization front. Osteoblast_sentence_95

Most bone surfaces express no new bone formation, no tetracycline uptake and no mineral formation. Osteoblast_sentence_96

This strongly suggests that facilitated or active transport, coordinated across the bone-forming group, is involved in bone formation, and that only cell-mediated mineral formation occurs. Osteoblast_sentence_97

That is, dietary calcium does not create mineral by mass action. Osteoblast_sentence_98

The mechanism of mineral formation in bone is clearly distinct from the phylogenetically older process by which cartilage is mineralized: tetracycline does not label mineralized cartilage at narrow bands or in specific sites, but diffusely, in keeping with a passive mineralization mechanism. Osteoblast_sentence_99

Osteoblasts separate bone from the extracellular fluid by tight junctions by regulated transport. Osteoblast_sentence_100

Unlike in cartilage, phosphate and calcium cannot move in or out by passive diffusion, because the tight osteoblast junctions isolate the bone formation space. Osteoblast_sentence_101

Calcium is transported across osteoblasts by facilitated transport (that is, by passive transporters, which do not pump calcium against a gradient). Osteoblast_sentence_102

In contrast, phosphate is actively produced by a combination of secretion of phosphate-containing compounds, including ATP, and by phosphatases that cleave phosphate to create a high phosphate concentration at the mineralization front. Osteoblast_sentence_103

Alkaline phosphatase is a membrane-anchored protein that is a characteristic marker expressed in large amounts at the apical (secretory) face of active osteoblasts. Osteoblast_sentence_104

At least one more regulated transport process is involved. Osteoblast_sentence_105

The stoichiometry of bone mineral basically is that of hydroxyapatite precipitating from phosphate, calcium, and water at a slightly alkaline pH: Osteoblast_sentence_106

In a closed system as mineral precipitates, acid accumulates, rapidly lowering the pH and stopping further precipitation. Osteoblast_sentence_107

Cartilage presents no barrier to diffusion and acid therefore diffuses away, allowing precipitation to continue. Osteoblast_sentence_108

In the osteon, where matrix is separated from extracellular fluid by tight junctions, this cannot occur. Osteoblast_sentence_109

In the controlled, sealed compartment, removing H drives precipitation under a wide variety of extracellular conditions, as long as calcium and phosphate are available in the matrix compartment. Osteoblast_sentence_110

The mechanism by which acid transits the barrier layer remains uncertain. Osteoblast_sentence_111

Osteoblasts have capacity for Na/H exchange via the redundant Na/H exchangers, NHE1 and NHE6. Osteoblast_sentence_112

This H exchange is a major element in acid removal, although the mechanism by which H is transported from the matrix space into the barrier osteoblast is not known. Osteoblast_sentence_113

In bone removal, a reverse transport mechanism uses acid delivered to the mineralized matrix to drive hydroxyapatite into solution. Osteoblast_sentence_114

Osteocyte feedback Osteoblast_section_11

Feedback from physical activity maintains bone mass, while feedback from osteocytes limits the size of the bone-forming unit. Osteoblast_sentence_115

An important additional mechanism is secretion by osteocytes, buried in the matrix, of sclerostin, a protein that inhibits a pathway that maintains osteoblast activity. Osteoblast_sentence_116

Thus, when the osteon reaches a limiting size, it deactivates bone synthesis. Osteoblast_sentence_117

Morphology and histological staining Osteoblast_section_12

Hematoxylin and eosin staining (H&E) shows that the cytoplasm of active osteoblasts is slightly basophilic due to the substantial presence of rough endoplasmic reticulum. Osteoblast_sentence_118

The active osteoblast produces substantial collagen type I. Osteoblast_sentence_119

About 10% of the bone matrix is collagen with the balance mineral. Osteoblast_sentence_120

The osteoblast's nucleus is spherical and large. Osteoblast_sentence_121

An active osteoblast is characterized morphologically by a prominent Golgi apparatus that appears histologically as a clear zone adjacent to the nucleus. Osteoblast_sentence_122

The products of the cell are mostly for transport into the osteoid, the non-mineralized matrix. Osteoblast_sentence_123

Active osteoblasts can be labeled by antibodies to Type-I collagen, or using naphthol phosphate and the diazonium dye fast blue to demonstrate alkaline phosphatase enzyme activity directly. Osteoblast_sentence_124

Osteoblast_unordered_list_0

  • Osteoblast_item_0_0
  • Osteoblast_item_0_1
  • Osteoblast_item_0_2
  • Osteoblast_item_0_3
  • Osteoblast_item_0_4

Isolation of Osteoblasts Osteoblast_section_13

Osteoblast_ordered_list_1

  1. The first isolation technique by microdissection method was originally described by Fell et al. using chick limb bones which were separated into periosteum and remaining parts. She obtained cells which possessed osteogenic characteristics from cultured tissue using chick limb bones which were separated into periosteum and remaining parts. She obtained cells which possessed osteogenic characteristics from cultured tissue.Osteoblast_item_1_5
  2. Enzymatic digestion is one of the most advanced techniques for isolating bone cell populations and obtaining osteoblasts. Peck et al. (1964) described the original method that is now often used by many researchers.Osteoblast_item_1_6
  3. In 1974 Jones et al. found that osteoblasts moved laterally in vivo and in vitro under different experimental conditions and escribed the migration method in detail. The osteoblasts were, however, contaminated by cells migrating from the vascular openings, which might include endothelial cells and fibroblasts.Osteoblast_item_1_7

See also Osteoblast_section_14

Osteoblast_unordered_list_2


Credits to the contents of this page go to the authors of the corresponding Wikipedia page: en.wikipedia.org/wiki/Osteoblast.