Bone Tissue Biochemistry
المؤلف:
Marcello Ciaccio
المصدر:
Clinical and Laboratory Medicine Textbook 2021
الجزء والصفحة:
p509-510
2025-12-16
48
Bone tissue consists of two main constituents: cells and the extracellular matrix. Compared to other tissues, the bone extracellular matrix is unique because it consists of an organic phase closely associated with a mineral phase. The organic phase consists of approximately 90% type I collagen and non-collagenous proteins. Although type I collagen is not specific to bone tissue as it is present in the skin, ligaments, and tendons, posttranslational modifications of the primary structure give it tissue-specific characteristics. Type I collagen is a protein formed by three filaments of about 1000 amino acids each, wrapped around each other to form an α-helix, which is synthesized as a precursor, the procollagen. The procollagen is excreted from the cell into the matrix, where specific enzymes remove the two globular ends, with the consequent formation of collagen that, without the globular ends, precipitates in the bone matrix and undergoes different maturation processes, including a process catalyzed by the enzyme lysine oxidase that determines the oxidation of lysine and hydroxylysine residues with the formation of cross-links of covalent type between the α chains of the same molecule and between adjacent molecules. Alongside this process, non-enzymatic mechanisms lead to the formation of glycation end products and racemization and isomerization phenomena at the terminal ends of the molecule. These modifications provide rigidity to the tis sue’s structure and increase the tissue’s resistance when subjected to intense stresses. The collagen deposited in the bone matrix is closely linked to other non-collagenous proteins, and after a specific interval of time from its deposition, it undergoes complete mineralization.
Osteoblasts and osteoclasts are the critical bone cells for producing biochemical markers of clinical interest. Osteoblasts, cells of mesenchymal derivation, are responsible for producing and depositing organic components of the matrix and activating the process of resorption of old bone tissue. Osteoclasts, large multinucleated cells derived from pluripotent cells of the monocyte/macrophage family, are responsible for the resorption of bone tissue. When activated, osteoclasts appear as polarized cells, with an apical zone containing mainly the cell’s nuclei and a basal zone characteristically jagged (ruffled border) attached to the surface of the bone matrix. Osteoclasts are equipped with specialized adhesion structures, called podosomes, which allow them to delimit the area of bone tissue where resorption will occur, preventing damage to the surrounding newly formed tissue. In this compartment, the osteoclast pumps, through ion channels, hydrogen and chlorine ions (reducing the pH to 5) and proteolytic enzymes, such as acid phosphatase, carbonic anhydrase, and cathepsin K, leading to the formation of a gap that will be filled by new bone matrix produced by osteoblasts.
Bone tissue undergoes continuous remodeling, a process in well-defined units known as BMU (Bone Metabolic Unit). Bone remodeling has different characteristics at different stages of life. From birth and throughout the growth period, the activity of osteoblasts is separated from that of osteo clasts both temporally and spatially, and consequently, the formation process prevails over that of the resorption. The bones increase their size and mass and assume the form and structure of the adult skeleton. Around the age of 20, for both sexes, about 95% of bone mass has developed, with the remainder being completed between the ages of 28 and 36 years. The final level of bone mass reached this point in life determines peak bone mass, the magnitude of which correlates with the risk of developing osteoporosis later in life. After skeletal maturity is reached, the activity of osteoblasts and osteoclasts is, in physiological situations, “coupled.” The formation/resorption balance is in equilibrium with the maintenance of skeletal mass. Following hormonal or other variations, starting from the peri-menopausal period in women and the fifth decade of life in men, the balance between the activity of osteoclasts and the activity of osteo blasts can be negative with the prevalence of the process of resorption over that of formation with progressive loss of bone mass. The whole process of bone remodeling is completed in 3–4 months and begins with the recruitment of osteoclast precursor cells to the site of resorption, under the action of cytokines and local growth factors. Osteoblasts play an essential role in osteoclastogenesis by producing stimulating factors, such as Receptor Activator of Nuclear factor-KappaB Ligand (RANKL) and osteoprotegerin, which, by preventing the action of RANKL on its osteoclas tic receptor RANK, prevents overproduction of osteoclasts and, consequently, inhibits resorption. This is followed by the phase of resorption of the old bone tissue by osteoclasts and the phase of formation of new bone tissue by osteoblasts. The different phases of bone remodeling are controlled by numerous systemic and local factors. Systemic factors include calcium-tropic hormones (parathormone, calcitonin, vitamin D), sex hormones, and glucocorticoids. Local fac tors include growth factors, cytokines, prostaglandins, and leukotrienes. The role of these factors is very complex because none of them act independently, and many act in synergy to regulate the delicate balance on which bone remodeling is based. The knowledge of this process is, however, fundamental to understanding the rationale behind the measurement of circulating biochemical markers that constitute the evidence of the coupling or decoupling of metabolic processes that, as a whole, define the phenomenon of bone remodeling or “bone turnover”.
These biochemical markers can be classified as biomarkers of bone formation, produced by the activity of osteo blasts, and biomarkers of resorption, produced by the activity of osteoclasts.
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