page_title: Osteoblast
section_title: Mineralization of bone
hierarchical_section_title: Osteoblast / Mineralization of bone
caption_attribution_description: This is a new figure created by user"Physio Muse" specifically to illustrate Osteoblast In the section Mineralization of bone and of its ancestral precursor, cartilage= It shows key features of osteoblasts within the bone forming unit, including bone mineral-forming transport mechanisms that are currently known.
context_page_description: Osteoblasts are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts function in groups of connected cells. Individual cells cannot make bone. A group of organized osteoblasts together with the bone made by a unit of cells is usually called the osteon.
  Osteoblasts are specialized, terminally differentiated products of mesenchymal stem cells. They synthesize dense, crosslinked collagen and specialized proteins in much smaller quantities, including osteocalcin and osteopontin, which compose the organic matrix of bone.
  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. The mineralized skeleton is the main support for the bodies of air breathing vertebrates. It is an important store of minerals for physiological homeostasis including both acid-base balance and calcium or phosphate maintenance.
context_section_description: The mechanisms of mineralization are not fully understood. Fluorescent, low-molecular weight compounds such as tetracycline or calcein bind strongly to bone mineral, when administered for short periods. They then accumulate in narrow bands in the new bone. These bands run across the contiguous group of bone-forming osteoblasts. They occur at a narrow (sub-micrometer) mineralization front. Most bone surfaces express no new bone formation, no tetracycline uptake and no mineral formation. 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. That is, dietary calcium does not create mineral by mass action.
  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.
  Osteoblasts separate bone from the extracellular fluid by tight junctions  by regulated transport. Unlike in cartilage, phosphate and calcium cannot move in or out by passive diffusion, because the tight osteoblast junctions isolate the bone formation space. Calcium is transported across osteoblasts by facilitated transport (that is, by passive transporters, which do not pump calcium against a gradient). 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. Alkaline phosphatase is a membrane-anchored protein that is a characteristic marker expressed in large amounts at the apical (secretory) face of active osteoblasts.
  At least one more regulated transport process is involved. The stoichiometry of bone mineral basically is that of hydroxyapatite precipitating from phosphate, calcium, and water at a slightly alkaline pH:
                6 HPO₄²⁻ + 2 H₂O + 10 Ca²⁺ ⇌ Ca₁₀(PO₄)₆(OH)₂ + 8 H⁺
  In a closed system as mineral precipitates, acid accumulates, rapidly lowering the pH and stopping further precipitation. Cartilage presents no barrier to diffusion and acid therefore diffuses away, allowing precipitation to continue. In the osteon, where matrix is separated from extracellular fluid by tight junctions, this cannot occur. 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. The mechanism by which acid transits the barrier layer remains uncertain. Osteoblasts have capacity for Na⁺/H⁺ exchange via the redundant Na/H exchangers, NHE1 and NHE6. 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.
caption: Major features of the bone-forming complex, the osteon, composed of osteoblasts and osteocytes.
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