Procollagen cross-links

Blood Alkaline phosphatase (bone-specific) Osteocalcin Procollagen type I carboxy-terminal propeptide (PICP) Procollagen type I amino-terminal propeptide (PINP) Procollagen type III amino-terminal propeptide (PIIINP) Blood Acid phosphatase (acid-resistant) Type I collagen carboxy-terminal telopeptide (ICTP) Urine Calcium Hydroxyproline Cross-linked peptides (pyridinium and deoxypyridinoline)... 

Figure 3.4 Factors affecting foreign body reaction and potential points of intervention at the level of the myofibroblast (1) inhibit synthesis or release of TGF-P (2) block stimulation by TGF-P of its membrane receptors on the activated fibroblast (3) inhibit the Smad proteins, which transfer the TGF-P effect to the nucleus (4) inhibit transcription of procollagen mRNA (5) inhibit translation of the message to form procollagen (6) inhibit prolyl-4-hydroxylase, which creates hydroxyproline and facilitates helix formation (7) inhibit lysyl oxidase, which cross-links the collagen (8) enhance the function of MMPs, which degrade collagen, or inhibit TIMPs, which degrade MMPs.

Fig. 4. Role of the extension peptides in the folding and secretion of procollagen. Once secreted out of the cell, the extension peptides are removed and the resulting tropocollagen molecules aggregate and are cross-linked to form a microfibril.

Inter- and intramolecular carbohydrate bridge Fio. 12. Structures of cross-links in procollagen and collagen. From Hermann (1960b),... 

Alignment of procollagen VII into cysteine cross-linked hexamers (triple helical dimers)... 

The synthesis of fibrillar collagen (e.g., types I, II, and III) begins Inside the cell with the chemical modification of newly made a chains and their assembly Into triple-helical procollagen within the endoplasmic reticulum. After secretion, procollagen molecules are cleaved, associate laterally, and are covalently cross-linked Into bundles called fibrils, which can form larger assemblies called fibers (see Figure 6-20). 

Musculoskeletal In ASSERT, a multicenter, open, 96-week study, 385 antiretroviral drug-naive adults with HIV infections were randomized to either abacavir -I- lamivudine or tenofovir-I-emtricitabine with efavirenz [60 ]. There was reduced bone mineral density in both groups, but to a greater extent with the latter (hip 1.9% versus 3.6% lumbar spine 1.6% versus 2.4%). Loss of at least 6% was more common in those who took tenofovir-I-emtricitabine (13% versus 3%). Markers of bone turnover (osteocalcin, procollagen 1, N-terminal propeptide, bone-specific alkaline phosphatase, and type 1 collagen cross-linked C telopep-tide) increased in both groups during the first 24 weeks and stabilized or improved thereafter, but without complete resolution. 

In the extracellular space, procollagen is further modified by enzymes which cut the C- and N-terminal portions of the molecule and make tropocollagen suitable for self-assembly into banded fibrils. The last enzymatic modification of the collagen molecule is by lysyl oxidase, which initiates a series of reactions leading to the formation of stable intermolecular cross-links. As far as lysyl oxidase is concerned, in vivo, this enzyme activity in rat skin does not seem to be significantly affected by excess of vitamin C in the diet on the contrary, lysyl oxidase was inhibited in a concentration-dependent manner in an in vitro assay in which lysyl oxidase activity of chick embryo bones was measured in the presence of increasing concentrations of ascorbic acid (Quaglino et aL, 1991). A similar reduction was also observed by Paris et al. (1984) in cultures of rabbit aortic smooth muscle cells. 

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