Anatomical structures of bones
Bone forms the skeletal system and forms for vertebrates as support for an internal structural system, grow and has variation in size and shape to have a capacity to withstand the mechanical vigor, also the bone is looked as an inorganic ions main source, and efficiently takes part in the balance of calcium/phosphate of body and it is a tissue constantly formed and throughout life it can be remodeled.
Also bone formed from organic matrix , cells and water and inorganic minerals, composed by the crucify of the matrix catching osteoblasts to become later osteocytes (Roux and Orcel,2000).Bones are hollow with criss-crossing struts for structural strength and the number of hollow bones varies among species (Ritchison, 2007). Within the bones hollow air spaces are directly joined to the respiratory system, reinforcing efficiency of respiratory system.
There are some influence of flight on bird skeletons, but it is not merely have a role on its design (David and McFarland, 2010).The medullary bones such as the tibia , femur , pubic bones ribs , ulna , toes and scapula are an serious source of calcium for laying that acts in shells of egg as a primary component (Jacob and Pescatore,2013). Bones can be in general distinguished into five types: long bones such as femur, tibia, ulna and radius that have two extremities or epiphysis and diaphysis ,a tube as cylindrical form in the middle and a transitional zone between them (metaphysis) (Fayez et al.,2009 ).
The epiphysis and the diaphysis in growing long bone, come from freelance centers of ossification and are discrete by a cartilage layer, known as the epiphyseal or growth plate (Brown and DeLuca,1992; Casinos and Cubo , 2001). While the short bones in hand as carpal and tarsal bones are often cubiform, and have in compact bone just a thin layer of be all around a spongy or trabecular bone interior (Cowin ,2004) . Flat bones as skull, sternum and capula that are supposed in compact bone contain inner and outer tables with trabecular bone (diploe) between the two tables (Tam et al.,2006). The bones with irregular shaped consist in compact bone an outer thin layer incased spongy bone in inner region of it, the scapula is the example of an irregular bone (Brent and Tabin,2002). The sesamoid bones as patella and pisiform are a short bones that are included in tendons. (Kose et al., 2012).
2.2 Histological structure of bone
On collagen fiber arrangements, bone tissue can be classed into two various kinds: woven bone and lamellar bone , also classed into compact bone and trabecular bone(Hernandez,2004).Woven Bone is a random collagen, with large numbers of osteoblasts and osteoprogenitor cells close to the side of them(Fayez et al.,2009 ). Despite of the woven bone is the main bone kind in the developing fetus, and lamellar (mature) bone is the main kind of bone in the adult, in adults, immature bone areas are also found, particularly in site in which bone is remodeled (Doblar et al., 2004 ; Sandberg ,2013 ). Areas of woven bone are also showed orderly in tendons in region which put in into bones and in alveolar socket of the oral cavityin adult (Branstetter et al .,2012).Lamellar bone is a mature bone has a well- regular arrangement of collagen fibers in adult (Bunger et al., 2010; Kerschnitzki et al., 2011).The lamellar bone is formed when the deposition rate is slow (Uthgenannt et al ., 2007). The lamellae in the cortex are arranged in peripheral also tubular arrangements , the tubular form is called an osteon (Bach-Gansmo et al.,2015). Haversian canal is the central part of the tube and that includes blood and lymphatic vessels and nerves (Bromage et al.,2009 ; Mohsin et al., 2006).
The cortical bone mechanical supporting is achieved by osteons, when the long axis of an osteon is parallel to the long axis of a long bone (Hiller et al .,2003 ; Havill , 2003). Volkmann’s canals and Haversian systems (osteons) are of 4-6 lamellae (cylindrical units) that be all around a central Haversian canal , in thickness ,each lamella is several microns and its fibers occupy in a spiral pattern are surrounded the canal (Castrogiovanni et al.,2011).The Haversian canal includes venules ,capillaries, lymphatic vessels, and a loose connective tissue including osteoprogenitor cells(Carnelli , 2010). Haversian systems comprise a branched cylinders system that are organized surrounding branching vessels of blood, and consequently they are directed in the long axis of the bone(Wilfred et al ,. 2009). Volkmann’s canals are vascular channels join Haversian canals with them ,also join the Haversian system with the vessels of blood in the periosteum (Kumaravel , 2015). Canaliculi are large network organized in to the canal radially (Michales et al., 2010) The system of canaliculi have a function of the substances transit between the osteocytes and blood vessels after opens to the Haversian canal (Gururaja,2004 ; Bozal et al., 2012).
Compact Bone commonly contains of concentric lamellae organized into reiterated units of osteons or Haversian systems, interstitial lamellae between the Haversian systems, and inner and outer circumferential lamellae (Wojnar, 2010) .In spaces between these lamellar there are cells called osteocytes (Martiniakova et al., 2010).Compact mature bone is known as a lamellar bone because of its organization(Govsa et al ., 2013).
Trabecular bone is a bone spongy spicules in the marrow space and is also known spongy, medullary or cancellous bone , these trabecular bone spicule is consist of many lamellae (Harvey et al., 2015).Lamellae are ordinary organized as a longitudinal form in trabecular bone, and osteons are usually not formed( Hiller et al.,2003). The endosteal layer is rich with osteoclasts and osteoblasts (Raghu et al., 2012). Trabecular bone is more active in metabolism than compact bone , as a result, studies of bone metabolism are well done on this bone component (Martiniakova et al., 2010).
Bone consists principally of specialized cells ,osteoblasts, osteocytes and osteoclasts(Arnett, 2013). Osteoblasts produce bone tissue or bone formation (osteogenesis) and mineralization (Usui et al., 2008; Rensberger and Martínez , 2015). Osteoclasts are foremost in charge of bone resorption (René et al., 2015 ; Dale et al., 2015).
Osteocytes regulate this resorpoiton (René et al., 2015). Osteoblasts and osteocytes are derived from The differentiation of mesenchymal cells (Provot et al ., 2013), but the osteoclasts are originate from hematopoietic precursor cells and are associated with monocyte and macrophages(Mizoguchi et al., 2013).
Osteoblasts are progenitor cells recruited from the hematopoietic compartments, and then proliferate and differentiate toward mature osteoclasts , and thus have a necessary role in osteoclast characterization organization and regulation the majority of the bone matrix proteins and are in charge of activity of mineralization (Roux and Orcel, 2000) .
The origin of osteoblasts are the pedigree of mesenchymal multipotent stem cells which lead to to adipocytes, chondroblasts, fibroblasts and myoblasts (Skillington et al ,2002). In the osteogenic lineage ,the first step is the osteoprogenitor cells formation which present in the periosteum inner layer, the endosteum lining marrow cavities, osteonal (Haversian) canals, piercing Volkmann’s canals, and in perivascular tissue relative to bone (Hooper and Scott , 2005).
Osteoprogenitor cells found in the bone marrow and they are indiscernible from stromal cells of marrow (Javed, 2010).The distinct shapes of Osteoblasts are cuboidal or columnar with or without a nuclear clear zone lining surfaces of bone at regions of formation of active bone and in charge of type I collagen production and the proteoglycans (glycosaminoglycan) which largely consist form the organic component of bone matrix, also called osteoid ( Kazama et al ., 2011).
Osteoblasts participate in the osteoid subsequent mineralization by the matrix vesicles release and the phosphate and calcium deposition, and looked as exemplary cells-produce protein with an essential amount of rough endoplasmic reticulum, a abundant mitochondria and a large Golgi apparatus( Kogianni and Noble ,2007 ; Nakamura , 2007) .
The enzyme activity of alkaline phosphatase are earliest markers of the phenotype of osteoblast (Schiller et al, 2009). In addition to the proteoglycans production and type I collagen, osteoblasts can produce a differents of other non-collagenous proteins as osteocalcin,osteopontin , osteonectin and bone sialoprotein, these proteins also act as osteoblast phenotype markers and each has a model of expression during differentiation of osteoblast ( Nakamura, 2007).
Osteocytes are as stellate in shaped in the mineralized bone matrix which include 90-95% of bone cells, so that they form in the skeleton of adult the most numerous cell of bone. The osteoblast morphology, a full rounded shape polygonal cell, varies greatly as it becomes an osteocyte with decreased cytoplasm and abundant dendritic processes( Guo and Bonewald, 2009).
Osteocytes encased in small spaces within bones called lacunae, and are connected to one another by networks of cellular projections located inside tubes within bone called canaliculi (Schneider et al., 2011; Michael et al., 2013 ). There are several functions of osteocyte, containing osteolysis, sensing the strains produced in response to bones mechanical loading, and giving signals which influence the osteoblasts function and osteoclasts and, consequently, bone turnover (Kogianni and Noble, 2007 ; Guo and Bonewald ; 2009Nakamura et al., 2013 ; Dale et al., 2015 ; ). Osteoclasts are large multinucleate cells of hematopoietic origin of monocytes/ macrophage lineage in the bone marrow, thus comprise phagocytic properties (Zigdon-Giladi et al .,2015) and have well developing Golgi apparatus surround nuclei and abundant mitochondria and endoplasmic reticulum, and they come to lie within an enzymatically etched depression called Howslip`s lacuna , or resorption bay. Degradation of both organic and inorganic bone matrix is achieved by osteoclast (Rissanen, 2013). Small amounts of bone are resorbed during the bone remodeling by the activity of osteoclasts, followed by the induction of osteoblast precursors that differentiate and replace the amount of the removed bone, and during active bone resorption , the region of the cell that directly contacts the bony matrix has many infoldings that collectively from a ruffled border subtended by the vesicular zone , consisting primarily of vesicles, most of which are filled with lysosomal enzymes (Arnett, 2013).
Immediately peripheral to the ruffled border is a clear zone , exaggerated ectoplasmic area laden with cytoskeletal elements , especially actin filaments , and free of most organelles (Alatalo et al., 2000).This portion of the cytoplasm may be involved in assisting the attachment of the osteoclast to the bony matrix along the perimeter of the resorption bay.The bulk of the osteoclast`s cytoplasm , which houses most of the organelles and all of the nuclei , is called the basal zone (Kogiannim et al., 2008 ; Samuelson ,2007; Mulari et al., 2003).
2.3 Collagen fibers
Collagen is most numerous protein in connective tissues, elastin, glycosaminoglycans and proteoglycans. Collagens are proteins as a triple helix with chains of three component polypeptide alpha. There are several subtypes (types I to XIII) . Each other different in their biochemical structure and are a different gene product(Michelacci,2003).The several fibrillar types, basement membrane-related, fiber-related, and short chain define the collagen type.The most numerous collagen type is type I collagen in most connective tissues(Koch et al., 2001) .
large amounts of glycogen firstly demonstrated in hypertrophic cartilage cells just prior to ossification, but was unable to demonstrate the presence of glycogen in the osteoblasts or in highly vascularized bona (Gillespie et al., 2011).
Glycogen might be responsible for the preliminary accumulation of phosphate ions in calcification Hypertrophic cartilage cells provide both the phosphatase and the glycogen; the latter on hydrolysis produce hexose-phosphoric esters that are under the phosphatase action and the calcium of the circulating body fluids result to the insoluble phosphate deposition of calcium in the matrix (Kulaev et al. ,2005), therefore , glycogen may have some role in the mineral deposition in calcifying tissues, led to a renewed interest in the histochemistry of the presence of glycogen in areas of calcification ossification, and concluded that the amount of glycogen in the cartilage cells is proportional to their state of hypertrophy. (Omelon et al.,2013). From this it might first initiate the differentiation of the osseous tissue and later serve as a primary source of the phosphoric esters required for calcification (Gillespie et al., 2011).
During the formation of endochondral bone the glycogen is present in moderate amounts in the resting cartilage cells, that it increased in amount and became irregular in distribution in the hypertrophie cartilage cells, and that it disappeared abruptly when the cartilage became calcified(Bruckner et al.,1989) .
During the formation of hind limbs ,the presence of glycogen granules in the mesenchymal cells adjacent to the osteoblasts in endochondral formation, that the osteoblasts contained little or no glycogen although some of the newly-formed trabeculae showed rows of cells containing glycogen ( Schajowicz and Cabrini , 1954).
2.5 Alkaline phosphate
The presence of phosphatase in areas of primary bone development, and was thus able to establish a close relationship between the presence of phosphatase in cartilage and the calcification of the cartilage (Clarke, 2008) .
The phosphatase is responsible for the preliminary accumulation of phosphate ions in the process of calcification(Wang et al.,2000).The first signs of alkaline phosphatase activity in the development of endochondral bone appear in localized areas of the perichondrium. Subsequently, the cartilage adjacent to these areas gives an intense reaction both in the cells and in the matrix.
With the beginnings of ossification, the amount of alkaline phosphatase reaches its peak, and is present in the early osteoblasts, in the fibroblasts in the matrix as ossification progresses the amount of alkaline phosphatase increase (Bonucci , 2007).
The bone matrix calcifies when it is laid down, and that, under optimum conditions it is usually calcified simultaneously with its deposition (Anderson et al., 2004). Calcium hydroxyapatite is the essential mineral form. The calcium carbonate is the mineral most prevalent that present in invertebrates, while the oxalate is common in plants (Weiner and Dove 2003).
Calcification occurs in many different situations in the body. Firstly, cartilage physiologic process and osteoid mineralization. Secondly, a pathologic extracellular or intracellular calcification that take place in relation with tissue damage.Thirdly, a metastatic calcification, that happens in relation with levels of changing of calcium serum and phosphate. Finally, there are the an abnormal crystal deposition diseases. (Fayez et al.,2009 ).
The mineralization initiation is a result of heterogeneous nucleation, the complexes of phosphate and calcium phosphate at the nucleation region in the matrix rather than by simple precipitation. In mature bone, it is likely which crystalline calcium carbonate including hydroxyapatite is deposited rather than an amorphous calcium phosphate or hydroxyapatite(Clarke , 2008).
2.7 Golgi elements
The size of the Golgi elements increased steadily as the osteoblasts matured, and the general mesenchyme (Clarke , 2008) Golgi element remained a discrete juxta-nuclear body throughout the life of the osteoblasts(Shitara et al., 2013). In the chondroblastic series of cells, the Golgi elements took a large size capping the nucleus.
Unlike the osteogenic series of cells, changes in the size of the element during the maturation of the chondroblasts were not found. There appeared to be a disintegration of the element during the hypertrophic stage(Glick and Nakano,2009).
The mitochondria were most numerous in large osteoblasts, in which they occupied every part of the cytoplasm except the juxta-nuclear vacuole, and generally tended to be orientated in the long axis of the cell (Downey and Siegel ,2006).In the development of cartilage , the mitochondria were most numerous in the perichondrial cells. In both the osteoblastic and chondroblastic series of cells, the mitochondria were most numerous where the rate of deposition of intercellular matrix was greatest. The mitochondrial content of the reticular cells,mesenchymal cells, and of the osteoblasts was increased as these cells became osteoclasts. Chang stated that the osteoclasts contained more mitochondria than any other cell in the bone area formation(Downey and Siegel ,2006 ; Coe, 2008).
2.9 Embryonic Origin of Skeleton
Vertebrate skeletons have two distinct embryological origins from two of the four germ layers, the two being mesoderm and neural crest (Hall and Gillis, 2013). The skeletogenic mesenchyme come from these layers from which cartilage and bone originate: in the trunk – limbs, primarily mesoderm for endoskeleton, vertebrae and ribs – but with contributions to the base of the skull; and neural crest for head and branchial region exoskeleton and endoskeleton (Hall , 2014) .
The neural crest also results odontogenic or tooth-forming mesenchyme from which dentine and other mesenchymal tissues like alveolar bone and the periodontal ligament orginate ( Hall , 2014 ; Isern et al., 2014 ).
In the embryo ,skeletogenic cells do not orginate in the site where skeletal tissues will form (Lefebvre and Bhattaram , 2010) .
Migration of cell is most spacious from the neural crest, while somites produce the cells that will form the vertebrae migrate a substantial distance the to enclose the axial notochord and spinal cord. Likewise, cells that form the ribs migrate some distance from the somites ( Helms and Schneider, 2003).
The vertebrae origins ,it is suitable to start with the subdivision of paraxial mesoderm development, segmentation and subsequent into presomitic mesoderm, pairs of somites, and finally into sclerotome, dermotome and myotome (Hawke and Garry , 2001 ; Hirst and Marcelle, 2015) .
There is a topographical relation between sclerotomal cells as they migrate away from the dermotome and myotome ,dermomyotome, which form connective tissue and muscle, and the notochord and spinal cord as they seem in an embryonic chick which incubate for 50 hours(Docker, 2000 ; Christ et al., 2004; Nagashima et al., 2005).
The vertebrate skeleton is consists of two essential subdivisions: axial and appendicular components (Mead and Yutzey , 2009; Hostikka et al. ,2009) .The axial skeleton includes the skull, spine, sternum, and ribs, while the appendicular skeleton defines the bones of the extremities (Nakashima and Crombrugghe, 2003).The skull, per contra, is well considered as composing of two units: the chondrocranium , the elements at begin develop in cartilage and contains the cranial base and capsules enclosing the inner ears and nasal organs, the cranial vault and most of the upper facial skeleton,that originate from the direct diversion of undifferentiated mesenchymal cells into bone (Lieberman et al., 2000; McCarthy , 2001).
Skeletal cells are orginate from three distinguished embryonic cell lineages: neural crest cells share to the craniofacial skeleton; sclerotome cells from produce to the axial skeleton; and mesoderm cells of lateral plate form the appendicular component (Beppu et al. ,2000 ;Ohnishi et al.,2014; Graham et al.,2014 ).
Cells from these lineages contribute in the skeletogenesis process in four distinguished phases: (1) the cells migration to the region of future skeletogenesis skeletogenesis, (2) the epithelial–mesenchymal interaction which leads to (3) the condensations formation, and (4) the outright chondroblasts differentiation or osteoblasts (Hall and Miyake, 2000 ; Fujimaki et al., 2013).Formation of bone orginate from a cartilaginous template is indicated to as endochondral ossification(Leucht et al.,2008). This is a complex, many steps process demanding the consecutive formation and degradation of cartilaginous structures which act as templates for the developing bones(Lauder, 2000).Calcified bone formation on a cartilage scaffold, however, happen not only during skeletogenesis, but is also an whole part of postnatal growth, modeling of bone, and repair of fracture (Khanarian et al .,2012). Intramembranous bone varies from the endochondral component in which it is produced in the a cartilaginous blastema absence, rather, it originates immediately from mesenchymal cells condensing at centers of ossification and became transformed directly into osteoblasts (Hall and Miyake. 2000 ; Yoshida, 2000 ; Bailey et al., 2001 ; Bukka et al.,2004 ).
2.10 Ossification ( Bone Formation )
The axial and appendicular skeleton bones are formed by one of two processes, formation of intramembranous or endochondral bone.The primary variation between these two processes is the cartilaginous intermediary absence or presence.In the formation of intramembranous bone, bone is formed in the cartilage model absence, whereas in formation of endochondral bone, a cartilage model is first formed and then substituted by bone tissue(Forriol and Shapiro , 2005 ; Shapiro , 2008).
2.10.1 Intramembranous Bone Formation (Membranous)
The intramembranous ossification is responsible of formation of skull flat bones and face. Osteoprogenitor cells that orginate to osteoblasts and osteocytes are found within the mesenchyme (Forriol and Shapiro, 2005; Rivas and Shapiro, 2002). These cells assemble at the region in which new bone formed and differentiate into osteoblasts which efficiently make new matrix of bone.Intramembranous bones growth happens by apposition (deposition upon prior bone) of osteoblasts lining the of growing bones surfaces.
The centers of ossification develop within the bone and reinforce the mineralization rates (Nah et al ., 2000).As the adult growth, Haversian remodeling happens.Chondroid bone has been found within the skull, taking place in combination with suture closure(Van der Kraan et al., 2002; Ma et al., 2003 ; Kranioti et al., 2009) . This bone type has a histological intermediate between cartilage and bone, including types I and II collagen (Gillis et al., 2006).Chondroid bone forms a scaffold upon which lamellar bone is deposited. It is not substituted by bone as happens in the endochondral mode(Witten and Hall, 2002, 2003 ; Coathup et al., 2013).
2.10.2 Endochondral Bone Formation (Cartilage Model)
Endochondral ossification includes the cartilage tissue formation from whole mesenchymal cells and the subsequent surrogate of this cartilage tissue by bone tissue (Li et al., 2012) .
All of the skeletal components of the vertebral column, the pelvis, and the appendicular skeleton (limbs) develop via endochondoral ossification (De Crombrugghe et al., 2001).
The endochondral ossification process is classified into five stages(Wu et al .,2008; Farrell et al., 2011).
First, the mesenchymal cells are obliged to become cartilage cells. During the second phase of endochondral ossification, the obliged mesenchymal stem cells condense to compact nodules and distinguish into chondrocytes.During the third phase of endochondral ossification, chondrocytes increase quickly to form the cartilage model that will finally be substituted by bone tissue. As they divide, chondrocytes secrete a cartilage- specific extracellular matrix.
In the fourth phase, the chondrocytes become hypertrophic after stop dividing. Hypertrophic chondrocytes have proliferated formation of collagen type X and fibronectin, thus changing the residual of cartilage matrix ,therefore, it can be mineralized by calcium carbonate. At end, in the fifth phase, blood vessels start the cartilage model infestation. The hypertrophic chondrocytes succumb apoptosis and the ingrowing blood vessels invade spaces (Gibson et al., 2001). When the cartilage cells die, osteoprogenitor cells differentiate into osteoblasts and start to place down bone matrix on the partially-degraded, residues of mineralized cartilage (Aubin et al., 2006 ; Nakamura et al., 2010) .
The region at the cartilaginous model center in which ossification first happen is called as the primary center of ossification ( Gibson et al., 2001; Taniguchi et al . ,2007). ultimately, bone replaced all the cartilage , therefore, the cartilage tissue act as intervening model for the bone which will lastly replace it (Church and Langton, 2001).This process diffusions longitudinally from the primary ossification center to the ends of the bone. A secondary ossification center forms, keeping a cartilaginous growth plate between each epiphysis and the primary ossification center (Zelzer et al., 2002;Mackie et al., 2008 ; Staines et al., 2013). Once these secondary ossification centers form, there remains an cartilage area between the primary and secondary ossification centers.
The secondary ossification center turn to the epiphysis and the primary center to the diaphysis(Mackie et al., 2008 ; Raducanu, 2009; Song et al., 2007).The intervening cartilage is the epiphyseal growth plate and it is here which continued growth in length happens at both developing bone ends. The epiphyseal plates include three regions: chondrocyte proliferation region, a region of maturation of chondrocyte, and hypertrophic chondrocytes region (Aszodi et al., 2003 ). A complex series of events happen in the growth plate as the proliferate of resting chondrocytes, mature and become directed in columns. When the cells hypertrophy at the spending of the intervening cartilaginous matrix, the cartilage matrix becomes calcified. The calcified cartilage residues that then acts as a scaffold for the bone matrix deposition by osteoblasts( Brehm et al., 2006 ; Olszta et al., 2007 ; Shapiro , 2008; Hoemann et al ., 2010 ; Harvanová et al., 2014 ).The blood vessels pervade the spaces which left behind by the apopototic hypertrophic chondrocytes, a decisive happening in the new bone tissue formation (Zelzer and Olsen ,2005 ; Kanczler and Oreffo, 2008).
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