Biological Chemistry - Berezov, T. T., Korovkin, B. F. 1998

Bone Tissue
Bone Formation

The formation of the intercellular substance and the mineralization of Bone tissue result from The activity of bone-forming Cells known as osteoblasts. As bone tissue forms, these cells become embedded within the intercellular substance and transform into osteocytes. It is well established that bone serves as the body's primary calcium reservoir and plays an active role in calcium METABOLISM. Calcium release is achieved through bone destruction (resorption), whereas its binding occurs through bone formation. This underlies the continuous remodeling process of bone tissue that persists throughout an Organism's lifespan. In this process, bone shape adapts to changing mechanical loads. Remarkably, the human skeletal bone tissue is almost completely remodeled every 10 years.

Investigating The Mechanism of ossification remains a highly relevant area of study. The mineralization process requires strictly oriented Collagen fibers. As noted earlier, the direct formation of collagen fibers occurs in the extracellular space through the specific cross-linking of tropocollagen molecules. X-Ray Diffraction Analysis and Electron Cell/15.html">Microscopy have demonstrated that collagen fibers exhibit a cross-striation pattern with a 68 nm periodicity. Consequently, the repeat period of the fiber's Structure (striation) is severalfold shorter than the length of the constituent tropocollagen molecules. This proves that adjacent rows of tropocollagen molecules are not positioned directly on top of one another. In other words, each row of tropocollagen is staggered relative to the neighboring row by approximately ¹/₄ of the molecular length. As a result, the Structural Organization of a collagen fiber is based on parallel rows of tropocollagen molecules arranged in a quarter-staggered pattern. Another structural feature of collagen fibers is that the tropocollagen molecules within a row are not linked end-to-end; a gap exists between the end of one molecule and THE START OF the next. This gap plays a critical role in bone formation. It is highly probable that the gaps along the rows of tropocollagen molecules serve as the initial nucleation sites for the deposition of the mineral components of bone tissue.

The crystals formed within the collagen zone subsequently act as mineralization nuclei, where hydroxyapatite is deposited in the spaces between collagen fibers.

Research has shown that during bone formation in the calcification zone, Proteoglycans undergo degradation with the participation of lysosomal proteinases. As bone tissue mineralizes, hydroxyapatite crystals effectively displace not only proteoglycans but also Water. Dense, fully mineralized bone is virtually dehydrated. Under these conditions, collagen accounts for approximately 20% of the mass and 40% of the volume of bone tissue, with mineral components making up the remainder.

It should be noted that not all collagen-containing Tissues in the body undergo ossification. Apparently, specific inhibitors of calcification exist. A number of researchers believe that the continuous presence of proteoglycans in tissues such as Skin, tendons, and vascular walls prevents the mineralization of collagen. There is also the view that inorganic pyrophosphate may act as a calcification inhibitor. During tissue mineralization, the inhibitory effect of pyrophosphate is eliminated by pyrophosphatase, which has been detected in bone tissue, among others. Overall, the Biochemical Mechanisms of bone tissue mineralization warrant further investigation.

The Catabolism of the bone matrix is likewise a complex process. Under both physiological and pathological conditions, bone resorption occurs, involving the virtually simultaneous breakdown («removal») of both mineral and organic bone structures. A certain role in the removal of mineral salts is played by the increased Production of organic acids, including lactate, during osteolysis*. It is well known that a shift in tissue pH toward the acidic side promotes mineral dissolution and, consequently, their removal.

The resorption of the organic matrix requires the presence and action of appropriate Enzymes. Chief among these are lysosomal acid Hydrolases, which exhibit a remarkably diverse spectrum in bone tissue. The Role of acid hydrolases in organic matrix catabolism involves the intracellular Digestion of fragments derived from resorbed structures.

Consequently, for intracellular Hydrolysis to take place, the structures of the organic matrix must first undergo Processing that yields polymer fragments. For instance, the resorption of collagen fibers requires the prior action of collagenolytic enzymes. Until recently, it was believed that collagenase was absent in animal tissues; however, a number of researchers have proven the presence of collagenolytic enzymes in certain animal tissues, particularly in bone.

* Osteolysis is the resorption of an area of organic bone tissue without subsequent replacement by another tissue.