Protein residues, bone

A key to the development of osteoblasts appears to be an osteoblast-specific transcription factor OS/2 or Cbfal.693-695 Mutations in human Cbfal are linked to a series of skeletal defects.696 A unique change accompanying conversion of a precursor cell into an osteoblast is the formation of a 49-residue y-carboxyglutamate (Gla)-containing protein called osteocalcin.697 (See also Box 15-F). It is the most abundant noncollagenous protein of bone. Its three Gla residues doubtless help to bind calcium ions and osteocalcin may be an initiator of crystallization. Osteocalcin has also been found in fish scales.698 Also present in bone is a 74-residue matrix Gla protein which has 5 Gla residues.699... 

Osteocalcin is a vitamin K-dependent protein of bone, which also occurs, to a small extent, in the bloodstream. Plasma osteocalcin occurs at 10-12 mg/liter blood plasma. The protein is very small and consists of only 46-50 amino acids (about 5700 Da), and thus is a very small protein. Several forms of osteocalcin exist, and these have cither two or three residues of CL A. 

Fig. 10.34 shows the INS spectrum of ox femur as the organic component is progressively removed [83]. Fig. 10.34a is very similar to that of the protein Staphylococcal nuclease. Fig 10.32, and emphasises one of the problems of working in this field because proteins are largely made of the same monomers (amino acids), the INS spectra of very different proteins tend to look very similar. Removal of the fat results in little change in the spectrum, Fig. 10.34b. It can be seen that elimination of the protein is highly effective, Fig. 10.34c the C-H stretching modes just below 3000 cm" and the C-H deformation modes at 1200-1500 cm have both disappeared. There is a weak, broad peak at 630 cm and its overtone near 1300 cm. For comparison, the INS spectrum of a highly crystalline reference hydroxyapatite is shown in Fig. 10.34d. The frequency match of the of the residual bone peak and that of the hydroxyapatite is exact, the width of the peak is attributed to heterogeneous broadening. The spectrum demonstrates that hydroxyl groups are still present in bone.

Noncollagenous Ca2+-binding proteins bind to bone minerals. They contain stretches of y-glutamic acid residues necessary for Ca2+-binding. 

Histones are small, basic proteins required to condense DNA into chromatin. They have been first described and named in 1884 by Albrecht Kossel. There are five main histones HI, H2A, H2B, H3 andH4. An octamer of core histones H2A, H2B, H3 andH4 is located inside a nucleosome, the central building block of chromatin, with about 150 base pairs of DNA wrapped around. The basic nature of histones, mediated by the high content of lysine and arginine residues, allows a direct interaction with the acidic phosphate back bone of DNA. The fifth histone HI is located outside at the junction between nucleosomes and is referred to as the linker histone. Besides the main histones, so-called histone variants are known, which replace core histones in certain locations like centromers. 

In bone, three proteins have been described which are vitamin K-dependent, osteocalcin (bone Gla protein), matrix Gla protein (MGP), and protein S. Osteocalcin is synthetized by osteoclasts, regulated by the active form of vitamin D, calcitriol. Its capacity to bind calcium needs a vitamin K-dependent y-carboxylation of three glutamic acid residues. The calcium binding capacity of osteocalcin indicates a possible role in bone mineralization, but its exact function is still unclear. However, it is widely used as a serum marker for bone mineralization. Protein S, mainly a coagulant, is also vitamin-K dependent and synthesized in the liver. Children with... 

Osteocalcin (bone Gla protein) Contains y-carboxyglutamate residues that bind to hydroxyapatite. Bone-specific. 

Silk fibers or monolayers of silk proteins have a number of potential biomedical applications. Biocompatibility tests have been carried out with scaffolds of fibers or solubilized silk proteins from the silkworm Bombyx mori (for review see Ref. [38]). Some biocompatibility problems have been reported, but this was probably due to contamination with residual sericin. More recent studies with well-defined silkworm silk fibers and films suggest that the core fibroin fibers show in vivo and in vivo biocompatibility that is comparable to other biomaterials, such as polyactic acid and collagen. Altmann et al. [39] showed that a silk-fiber matrix obtained from properly processed natural silkworm fibers is a suitable material for the attachment, expansion and differentiation of adult human progenitor bone marrow stromal cells. Also, the direct inflammatory potential of silkworm silk was studied using an in vitro system [40]. The authors claimed that their silk fibers were mostly immunologically inert in short and long term culture with murine macrophage cells. 

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