Urinary Excretion Levels of Hydroxylysine Glycosides in Osteoporotic Patients.

Mochidome, Naritoshi; Hara, Takashi; Osada, Satoru; Takayama, Akinori; Nagata, Minoru

doi:10.1248/bpb.17.836

Cited by 7 publications

(4 citation statements)

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“…However, the function of the sugar moieties and the factors which determine the level of glycosylation remain elusive. It was reported that the urinary excretion levels of hydroxylysine glycosides, especially GH, in osteoporotic patients were indirectly related to fractures in bone in osteoporosis [37]. Studies on fibrillar collagens have indicated that the hydroxylysyl‐linked sugar units in collagens may play a role in the control of organization of the fibrils [38, 39].…”

Section: Discussionmentioning

confidence: 99%

The glycosyltransferase activities of lysyl hydroxylase 3 (LH3) in the extracellular space are important for cell growth and viability

Wang

Kovanen

Raudasoja

et al. 2009

J Cellular Molecular Medi

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Lysyl hydroxylase (LH) isoform 3 is a post-translational enzyme possessing LH, collagen galactosyltransferase (GT) and glucosyltransferase (GGT) activities. We have demonstrated that LH3 is found not only intracellularly, but also on the cell surface and in the extracellular space, suggesting additional functions for LH3. Here we show that the targeted disruption of LH3 by siRNA causes a marked reduction of both glycosyltransferase activities, and the overexpression of LH3 in HT-1080 cells increases hydroxylation of lysyl residues and the subsequent galactosylation and glucosylation of hydroxylysyl residues. These data confirm the multi-functionality of LH3 in cells. Furthermore, treatment of cells in culture medium with a LH3 N-terminal fragment affects the cell behaviour, rapidly leading to arrest of growth and further to lethality if the fragment is glycosyltransferase-deficient, and leading to stimulation of proliferation if the fragment contains LH3 glycosyltransferase activities. The effect is reversible, the cells recovering after removal of the glycosyltransferase-deficient fragment. The findings were confirmed by overexpressing the full-length LH3 in native or mutated forms in the cells. The data indicate that the increase in proliferation depends on the glycosyltransferase activity of LH3. The overexpression of a glycosyltransferase-deficient mutant or targeted disruption of LH3 by siRNA in cells results in abnormal cell morphology followed by cell death. Our data clearly indicate that the deficiency of LH3 glycosyltransferase activities, especially in the extracellular space, causes growth arrest revealing the importance of the glycosyltransferase activities of LH3 for cell growth and viability, and identifying LH3 as a potential target for medical applications, such as cancer therapy.

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Section: Discussionmentioning

confidence: 99%

The glycosyltransferase activities of lysyl hydroxylase 3 (LH3) in the extracellular space are important for cell growth and viability

Wang

Kovanen

Raudasoja

et al. 2009

J Cellular Molecular Medi

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“…An alterable proportion of HYL residues are glycosylated to GGHYL form, and this specific form is abundant in bone type-Icollagen (Al-Dehaimi et al, 1999). Upon collagen degradation, both GGHYL and GHYL are released into the circulation (Kuo and Chen, 2017) and are excreted directly in urine as they are not metabolized in the liver or kidney (Yoshihara et al, 1994). Therefore, they can be comfortably quantified by high-performance liquid chromatography (HPLC) without preanalytical hydrolysis (Kuo and Chen, 2017).…”

Section: Hydroxylysinementioning

confidence: 99%

“…The levels of urinary HYL glycosides excretion are not affected by diet and thus there is an inverse correlation of GHYL excretion level with bone mineral density. Therefore, the observation of the levels of urinary excretion of HYL glycosides and their ratio can easily be quantified as tissue is being degraded (Yoshihara et al, 1994).…”

Section: Hydroxylysinementioning

confidence: 99%

A Comprehensive Review on the Biomarkers of Bone Remodeling in Vitamin D Deficiency

Nagappan

Sureshkumar

2021

Indonesian J Pharm

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Vitamin D (Vit.D) has been well regarded as one of the essential micronutrients for several biological functions in humans, including bone structure and function. The deficiency of Vit.D due to various environmental, lifestyle, and genetic factors affect bone remodeling, including bone mineralization and resorption. Consequently, several changes occur in the level of biochemicals which are implied in bone remodeling, either directly or via secondary pathways. Intriguingly, the levels of these biomolecules are hypothesized to have a strong association with the prognosis of Vit. D deficiency (VDD) related health complications. However, the precise association of various bone turnover-derived biomolecules with VDD-related effects are largely elusive. Thus, the in-depth understanding of specific associations of VDD and bone mineralization, would establish novel bioanalytical approaches for early detection and devise alternative strategies to provide symptomatic clinical support to VDD patients. Hence this review collates the available literature to elucidate the association of various bone resorption biomarkers and their relevance to VDD.

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“…It is an important advantage that hydroxylysine is not affected by diet and that the only source of GLH is bone. Therefore, collagen degradation is more specific than OHP [62,63].…”

Section: Bone Resorption Markersmentioning

confidence: 99%

Bone markers

Konukoğlu¹

2019

Int J Med Biochem

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B one tissue is one of the hardest tissues in the body. It has 3 important functions: mechanical, protective, and metabolic. The mechanical functions of the skeletal muscles are to provide body movement based on attachment to the bones. Contraction allows body movement. The protective function of the bones is the armor provided to internal organs, such as those in the cranium and thorax. Finally, there is the process of hematopoiesis in the bone marrow. The metabolic function of bone provides for the storage of ions, such as calcium, phosphorus, sodium, and magnesium, and the maintenance of hemostasis of these minerals [1][2][3]. This paper is a discussion of new and novel bone markers and preanalytical factors that affect analytical methods. Bone tissue structureBone is a mineralized connective tissue composed of an organic and inorganic structure. The inorganic structure, or mineral structure, of bone is primarily hydroxyapatite Ca10 (PO4) 6 (OH) 2 crystals, as well as magnesium, carbonate, and fluoride. The majority of calcium in the body is in the bones (about 99%). Hydroxyapatite crystals provide resistance to bone [4,5]. The collagen fibrils are the element that provides strength, while hydroxyapatite crystals contribute hardness. The organic matrix forms about half of the dry weight of the bone. Collagen is the major protein of the organic matrix; non-collagen molecular (glycosaminoglycans and glycoproteins, etc.) constitute about 10% of the organic matrix. Although 80% to 90% of collagen is type 1 collagen, other collagen types (type 3, 5, 11, 13 collagen) also make up the matrix structure [2,6,7]. Non-collagen proteins, such as proteoglycans (chondroitin sulfate and proteoglycan), glycoproteins (alkaline phosphatase and osteonectin), glycoproteins containing arginine-glycine-asparagine, (osteopontin and bone sialoprotein), osteoprotogerin, and carboxylated (Gla) proteins (osteocalcin and matrix Gla protein), are also present [8,9].Objectives: Bone has a dynamic metabolism that includes modeling and remodeling activities. There is continuous communication between 3 types of bone cells; osteoblasts, osteoclasts, and osteocytes. Local stress factors, cytokines, and hormones play an important role in these relationships. The most important structural component of bone is type 1 collagen. During the formation and degradation of collagen, some compounds are secreted into the bloodstream, and in cases of diseases involving the bone, the quantity of these compounds increases both in blood concentration and urinary excretion. Some bone markers are secreted into the circulation during bone formation, and some are released into the circulation through bone resolution. Bone markers reflect changes in bone metabolism due to primary or secondary causes, rather than a specific bone disease. Some factors affecting the results should be considered during the evaluation of changes. These factors include preanalytical effects, such as age, gender, diurnal rhythm, and analytical problems. This review is a summary of the cur...

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Urinary Excretion Levels of Hydroxylysine Glycosides in Osteoporotic Patients.

Cited by 7 publications

References 0 publications

The glycosyltransferase activities of lysyl hydroxylase 3 (LH3) in the extracellular space are important for cell growth and viability

The glycosyltransferase activities of lysyl hydroxylase 3 (LH3) in the extracellular space are important for cell growth and viability

A Comprehensive Review on the Biomarkers of Bone Remodeling in Vitamin D Deficiency

Bone markers

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