Increased C-telopeptide Cross-linking of Tendon Type I Collagen in Fibromodulin-deficient Mice

Kalamajski, Sebastian; Liu, Cuiping; Tillgren, Viveka; Rubin, Kristofer; Oldberg, Åke; Rai, J.P.N.; Weis, Mary Ann; Eyre, David R.

doi:10.1074/jbc.m114.572941

Cited by 64 publications

(69 citation statements)

References 35 publications

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“…These results suggest that the phenotype seen in CypB KO tendon might be due mainly to altered Lys modifications rather than diminished P3H. Another possibility is that the altered posttranslational modifications of collagen in CypB KO may change its interaction with collagen-associated small leucine-rich proteoglycans, such as decorin, biglycan, and fibromodulin, resulting in defective fibrils (49,50).…”

Section: Discussionmentioning

confidence: 89%

Cyclophilin-B Modulates Collagen Cross-linking by Differentially Affecting Lysine Hydroxylation in the Helical and Telopeptidyl Domains of Tendon Type I Collagen

Terajima

Taga

Chen

et al. 2016

Journal of Biological Chemistry

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Covalent intermolecular cross-linking provides collagen fibrils with stability. The cross-linking chemistry is tissue-specific and determined primarily by the state of lysine hydroxylation at specific sites. A recent study on cyclophilin B (CypB) null mice, a model of recessive osteogenesis imperfecta, demonstrated that lysine hydroxylation at the helical cross-linking site of bone type I collagen was diminished in these animals (Cabral, W. A., Perdivara, I., Weis, M., Terajima, M., Blissett, A. R., Chang, W., Perosky, J. E., Makareeva, E. N., Mertz, E. L., Leikin, S., Tomer, K. B., Kozloff, K. M., Eyre, D. R., Yamauchi, M., and Marini, J. C. (2014) PLoS Genet. 10, e1004465). However, the extent of decrease appears to be tissue-and molecular site-specific, the mechanism of which is unknown. Here we report that although CypB deficiency resulted in lower lysine hydroxylation in the helical cross-linking sites, it was increased in the telopeptide cross-linking sites in tendon type I collagen. This resulted in a decrease in the lysine aldehyde-derived cross-links but generation of hydroxylysine aldehyde-derived cross-links. The latter were absent from the wild type and heterozygous mice. Glycosylation of hydroxylysine residues was moderately increased in the CypB null tendon. We found that CypB interacted with all lysyl hydroxylase isoforms (isoforms 1-3) and a putative lysyl hydroxylase-2 chaperone, 65-kDa FK506-binding protein. Tendon collagen in CypB null mice showed severe size and organizational abnormalities. The data indicate that CypB modulates collagen cross-linking by differentially affecting lysine hydroxylation in a site-specific manner, possibly via its interaction with lysyl hydroxylases and associated molecules. This study underscores the critical importance of collagen post-translational modifications in connective tissue formation.Collagens comprise a large family of structurally related extracellular matrix proteins (1). Among all of the genetic types of collagen identified, fibrillar type I collagen is the most abundant, providing tissues and organs with form and stability. It is a heterotrimeric molecule composed of two ␣1 chains and one ␣2 chain forming a long uninterrupted triple helix with short non-helical domains (telopeptide) at both N and C termini. One of the functionally important characteristics of collagen is its unique, sequential post-translational modifications of Lys residues. The modifications include hydroxylation and monoand diglycosylation of hydroxylysine (Hyl), 3 and oxidative deamination of Lys and Hyl in the N-and C-telopeptides followed by extensive covalent intermolecular cross-linking (2). It is now clear that defective Lys modifications of collagen cause and/or are associated with a broad range of connective tissue disorders, including Ehlers-Danlos syndrome type VIA (3), bronchopulmonary dysplasia (4), Kuskokwim syndrome (5), Bruck syndrome (6, 7), fibrosis (8), disuse osteoporosis (9), and cancer progression (10, 11). Our recent finding showed that a switch of collage...

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Section: Discussionmentioning

confidence: 89%

Cyclophilin-B Modulates Collagen Cross-linking by Differentially Affecting Lysine Hydroxylation in the Helical and Telopeptidyl Domains of Tendon Type I Collagen

Terajima

Taga

Chen

et al. 2016

Journal of Biological Chemistry

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“…The pattern given of collagen ␣ chains, ␤ dimers, and ␥ trimers is characteristic for different tissue types, and individual bands can be subjected to mass spectral analysis (26). Representative data for one 14-day control, two 21-day control constructs, and two 21-day BAPN-treated constructs are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Collagen ␣1(I) chains were excised as individual bands (as marked in Fig. 3B) and digested in-gel with trypsin for mass spectral analysis to assess C-telopeptide lysine hydroxylation levels as described earlier (26).…”

Section: H-3-2010-070)mentioning

confidence: 99%

Lysyl Oxidase Activity Is Required for Ordered Collagen Fibrillogenesis by Tendon Cells

Herchenhan¹,

Uhlenbrock²,

Eliasson³

et al. 2015

Journal of Biological Chemistry

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143

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Background: Lysyl oxidase catalyzes collagen cross-link formation, which is essential for mechanically strong collagen fibrils. Results: LOX inhibition stops early mechanical development of tendon constructs and leads to irregularly shaped collagen fibrils. Conclusion: Collagen cross-linking is essential for successful fibrillogenesis and regulates fibril shape. Significance: LOX activity is required in the control of collagen fibril architecture by a mechanism that remains to be explained.

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“…Periostin is a matricellular protein preferentially expressed in collagen-rich fibrous connective tissues, including bone, that coordinates the regulation of bone morphogenetic protein 1-mediated proteolytic cleavage of pro-LOX to active LOX [64]. Fibromodulin, a member of small leucinerich proteins, is known to interact with collagen and affect collagen cross-linking, molecular packing, and fibril diameter [65]. Recently, it has been reported that fibromodulin forms a complex with LOX and targets specific cross-linking sites of type I collagen [66].…”

Section: Collagen Cross-linkingmentioning

confidence: 99%

A paradigm shift for bone quality in dentistry: A literature review

Kuroshima

Kaku

Ishimoto

et al. 2017

Journal of Prosthodontic Research

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A B S T R A C TPurpose: The aim of this study was to present the current concept of bone quality based on the proposal by the National Institutes of Health (NIH) and some of the cellular and molecular factors that affect bone quality. Study selection: This is a literature review which focuses on collagen, biological apatite (BAp), and bone cells such as osteoblasts and osteocytes. Results: In dentistry, the term "bone quality" has long been considered to be synonymous with bone mineral density (BMD) based on radiographic and sensible evaluations. In 2000, the NIH proposed the concept of bone quality as "the sum of all characteristics of bone that influence the bone's resistance to fracture," which is completely independent of BMD. The NIH defines bone quality as comprising bone architecture, bone turnover, bone mineralization, and micro-damage accumulation. Moreover, our investigations have demonstrated that BAp, collagen, and bone cells such as osteoblasts and osteocytes play essential roles in controlling the current concept of bone quality in bone around hip and dental implants. Conclusion: The current concept of bone quality is crucial for understanding bone mechanical functions. BAp, collagen and osteocytes are the main factors affecting bone quality. Moreover, mechanical loading dynamically adapts bone quality. Understanding the current concept of bone quality is required in dentistry.

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Increased C-telopeptide Cross-linking of Tendon Type I Collagen in Fibromodulin-deficient Mice

Cited by 64 publications

References 35 publications

Cyclophilin-B Modulates Collagen Cross-linking by Differentially Affecting Lysine Hydroxylation in the Helical and Telopeptidyl Domains of Tendon Type I Collagen

Cyclophilin-B Modulates Collagen Cross-linking by Differentially Affecting Lysine Hydroxylation in the Helical and Telopeptidyl Domains of Tendon Type I Collagen

Lysyl Oxidase Activity Is Required for Ordered Collagen Fibrillogenesis by Tendon Cells

A paradigm shift for bone quality in dentistry: A literature review

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