Bones

Function of the skeletal system:

Skeletal system has several functions in the organism. As established before, storage is one of them. Protection, support and movement are other main functions that will not discuss here. Also red bone marrow, located in the long bones and being a source of cells constituting to blood, will not be discussed here.

 

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What makes up a bone:

1. Osteoid – extracellular matrix proteins. Mainly collagen type I which organizes into collagen fibers, giving bone strength and durability as well as providing a nidus for nucleation of bone mineralization. Other proteins comprising to osteoid are steocalcin and osteonectin. Both are important for mineralization process as both bind to hydroxyapatite (see below), helping in its nucleation. Osteocalcin binds calcium avidly due to its structure: it possesses three γ-carboxylated glutamic acid residues, which associate easily with Ca²⁺.  Moreover, fibronectin, thrombospondin, osteopontin and bone sialoprotein can be found in the osteoid.
2. Inorganic salts – the mineral component. Mainly hydroxyapatite crystals and calcium carbonate. Hydroxyapatite structure: 3Ca₃(PO₄)₂·Ca(OH)₂. The mineral is a salt of both calcium and phosphorus and gives bones not only strength but also provides a form of storage of both elements in question. Crystals are arranged along collagen fibers, strengthening the construction.
3. Cells – osteoblasts, osteoclasts and osteocytes. Osteoblasts are responsible for bone formation through secretion of osteoid proteins and calcification processes. Osteoclasts are multinucleate cells that are responsible for bone resorption. They have phagocytic abilities and utilize those to remodel the bone. Osteoblasts and osteoclasts are descendants from separate lineages. The former originates from undifferentiated mesenchymal cell while the later come from progenitor cells in bone marrow. Macrophages and monocytes originate from the same cells as osteoclasts do, explaining phagocytic abilities of osteoclasts. Osteocytes are mature osteoblasts that are surrounded by bony matrix. Their main role is to transfer minerals from the bone interior to the growth surfaces.

 

Bone types:

Long bones – e.g. tibia or humerous

Short bones – e.g. carpals

Irregular – e.g. vertebrae

Flat – e.g. skull or ribs

Sesamoid – e.g. patella

 

Organization of a bone (long bone):

Most outer layer, covering the diaphysis of the bone is called periosteum. It is made of irregular dense connective tissue. Osteoblasts and osteoblast precursors reside in this layer. Underneath periosteum lays osteoid layer (described above). Both layers cover bone matrix, which composition was discussed earlier. Osteoid and bone matrix together make up the cortex of the bone. It should be clarified that osteocytes reside in the cortex, and are connected through canaliculi with each other and with osteblasts. Matrix is organized into osteons: concentric tubes (termed lamellae) with haversian canal at the centre. Blood vessels run through haversian canal, supplying osteocytes in blood. Matrix layer can be more than one osteon dense. Beneath it lays trabecular (also termed cancellous) bone, which is spongy. Bone marrow resides in the cavity that is covered with trabecular bone. Both, osteoblasts and osteoclasts, can be present in the trabecular bone. Thanks to that, trabecular layer of the bone is constantly remodelled, undergoing bone turnover.

Both extremities of diaphysis as well as epiphysis of long bones are made mostly of trabecular bone. Cortical bone is specific to the diaphysis.

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Remodelling:

Process of remodelling of bone is an ongoing phenomenon. Annually 25% of trabecular and 3% of cortical bone is renewed. The process is regulated by PTH and vitamin D. Continuous secretion of PTH causes activation of osteoclasts while intermittent secretion of PTH results in osteoblasts activation. In either case, PTH acts on osteoblasts and osteoclast precursors. Depending on mode of secretion, osteoblasts begin exocytosis of Ca²⁺ and phosphate, leading to the mineralization of  bone, or secrete cytokines which activate osteoclasts and cause osteoclast progenitors to differentiate. Among cytokines secreted by osteoblasts, macrophage colony stimulating factor (M-CSF), interleukins and RANK ligand appear to play a central role. However, the exact signalling processes between osteoblasts and osteoclast lineages are still not well understood.

Once activated, osteoclasts attach to the bone matrix by its ruffled border and begin secreting H⁺ (through V-type H⁺ pump) and proteases. Acidic environment causes hydroxyapatite crystals to dissolve, releasing Ca²⁺ and phosphate. Proteases and other enzymes are responsible for bone matrix and osteoid dissolution. Once a pit is created, osteoclasts move to another place and osteoblasts take their place to fill the pit with fresh osteoid and bone matrix. Equilibrium of this process can shift to either side depending on PTH, vitamin D, Ca²⁺ and phosphate plasma levels and other factors. For instance, immediate effect of vitamin D is resorption of bone; however the net effect for organism is bone synthesis, mediated by increasing calcium levels.