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

For instance, in patients with fatty liver disease hydroxyapatite-coated titanium implants perform better as those not-coated with this material [2].

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.

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.

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

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

[9] 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.[1].

In turn osteoblasts may give rise to osteocytes in a process dependent on the vascular musculature of blood vessels in the bone [10].

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

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

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

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

[24][25] The primitive skeleton is cartilage, a solid avascular (without blood vessels) tissue in which individual cartilage-matrix secreting cells, or chondrocytes, occur.

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

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

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.

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

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

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

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

[31] 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.

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

[33][34][35] An important additional mechanism is secretion by osteocytes, buried in the matrix, of sclerostin, a protein that inhibits a pathway that maintains osteoblast activity.

[36] 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.

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