Bone tissue cellular functions

Bone is a porous tissue composite material containing a fluid phase, a calcified bone mineral, hydroxyapatite (HA), and organic components (mainly, collagen type). The variety of cellular and noncellular components consist of approximately 69% organic and 22% inorganic material and 9% water. The principal constiments of bone tissue are calcium (Ca ), phosphate (PO ), and hydroxyl (OH ) ions and calcium carbonate. There are smaller quantities of sodium, magnesium, and fluoride. The major compound, HA, has the formula Caio(P04)g(OH)2 in its unit cell. The porosity of bone includes membrane-lined capillary blood vessels, which function to transport nutrients and ions in bone, canaliculi, and the lacunae occupied in vivo by bone cells (osteoblasts), and the micropores present in the matrix. 

Erythropoietin stimulates erythroid proliferation and differentiation by interacting with erythropoietin receptors on red cell progenitors. The erythropoietin receptor is a member of the JAK/STAT superfamily of cytokine receptors that use protein phosphorylation and transcription factor activation to regulate cellular function (see Chapter 2). Erythropoietin also induces release of reticulocytes from the bone marrow. Endogenous erythropoietin is primarily produced in the kidney. In response to tissue hypoxia, more erythropoietin is produced through an increased rate of transcription of the... 

Copper The content of Cu in the human body is estimated to range between 50 and 80 pg. The RDA is 1.5-3.0 mg per day for adults. Copper is an essential component of several enzymes and is required in bone formation, cellular respiration, cardiac function, connective tissue development, and myelination of the spinal cord [11-14]. This metal is also necessary for Fe absorption and mobilization. Again, Cu content in milk differs with the biological species, stage of lactation, and diet intake. In all species colostrum is substantially richer in Cu than mature milk is. 

The clinical manifestations of serum phosphate depletion depend on the length and degree of the deficiency. Moderate hypophosphatemia of 1.5 to 2,4 mg/dL (0.48 to 0.77 mmol/L) is usually not associated with clinical signs and symptoms (unless chronic, when osteomalacia or rickets develops). Plasma concentrations less than 1.5 mg/dL (0.48 mmol/L) may produce clinical manifestations. Because phosphate is necessary for the formation of ATP, glycolysis and cellular function are impaired by low intracellular phosphate concentrations. Muscle wealmess, acute respiratory failure, and decreased cardiac output may occur in phosphate depletion. At very low serum phosphate (<1 mg/dL or <0.32 mmol/L), rhabdomyolysis may occur. Phosphate depletion in erythrocytes decreases erythrocyte 2,3-diphosphoglycerate, which causes tissue hypoxia because of increased affinity of hemoglobin for oxygen. Severe hypophosphatemia (serum phosphate concentration <0.5 mg/dL [<0.16 mmol/L]) may result in hemolysis of the red blood cells. Mental confusion and frank coma also may be secondary to the low ATP and tissue hypoxia. If hypophosphatemia is chronic, impaired mineralization of bone produces rickets in children and osteomalacia in adults. 

A second member of the parathyroid hormone family, parathyroid hormone-related protein (PTHrP), is quite similar to PTH in amino acid sequence and protein structure. Like PTH, it activates the parathyroid hormone receptor causing increased bone resorption and renal tubular calcium reabsorption. Increased serum concentrations of parathyroid hormone-related protein are the predominant cause of hypercalcemia in cancer patients with solid tumors. This observation led to its discovery and to the elucidation of its many cellular functions in normal tissues. In contrast to PTH, which is expressed only in parathyroid glands, PTHrP is detected in many tissues in fetuses and adults it is found in epithelia, mesenchymal tissues, endocrine glands, and the central nervous system. This protein is also the principal regulator of placental calcium transport to the fetus. 

Peptide Amphiphiles (PAs) present a promising solution for bone tissue engineering as they are able to be utilized in surface modification of devices for enhanced efficacy. For example, Sargeant et al. proposed employing PAs to functionalize ordinarily inert nickel titanium surfaces. Such modification can enhance native cellular attachment, minimize any adverse non-specific interactions, and improve stability through prevention of desorption, degradation, and molecular... 

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