Treatment of cartilage with β-aminopropionitrile accelerates subsequent collagen maturation and modulates integrative repair

McGowan, Kevin B.; Sah, Robert L.

doi:10.1016/j.orthres.2004.02.015

Cited by 23 publications

(23 citation statements)

References 33 publications

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“…Previously, BAPN treatment of cartilage explants and alginate hydrogels indicated a reduction in the stable incorporation of nascent collagen into the tissue ECM or gel microenvironment3031. Here, our results build on these existing bulk analyses and show that this defect in crosslinking manifests organizationally, with a buildup of matrix proteins in the immediate pericellular space, and a decrease in protein content further removed from the cell.…”

Section: Discussionsupporting

confidence: 83%

High fidelity visualization of cell-to-cell variation and temporal dynamics in nascent extracellular matrix formation

McLeod

Mauck

2016

Sci Rep

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Extracellular matrix dynamics are key to tissue morphogenesis, homeostasis, injury, and repair. The spatiotemporal organization of this matrix has profound biological implications, but is challenging to monitor using standard techniques. Here, we address these challenges by using noncanonical amino acid tagging to fluorescently label extracellular matrix synthesized in the presence of bio-orthogonal methionine analogs. This strategy labels matrix proteins with high resolution, without compromising their distribution or mechanical function. We demonstrate that the organization and temporal dynamics of the proteinaceous matrix depend on the biophysical features of the microenvironment, including the biomaterial scaffold and the niche constructed by cells themselves. Pulse labeling experiments reveal that, in immature constructs, nascent matrix is highly fibrous and interdigitates with pre-existing matrix, while in more developed constructs, nascent matrix lacks fibrous organization and is retained in the immediate pericellular space. Inhibition of collagen crosslinking increases matrix synthesis, but compromises matrix organization. Finally, these data demonstrate marked cell-to-cell heterogeneity amongst both chondrocytes and mesenchymal stem cells undergoing chondrogenesis. Collectively, these results introduce fluorescent noncanonical amino acid tagging as a strategy to investigate spatiotemporal matrix organization, and demonstrate its ability to identify differences in phenotype, microenvironment, and matrix assembly at the single cell level.

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Section: Discussionsupporting

confidence: 83%

High fidelity visualization of cell-to-cell variation and temporal dynamics in nascent extracellular matrix formation

McLeod

Mauck

2016

Sci Rep

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“…[62][63][64] Glycation in solution may also enhance integration with the surrounding tissue due to accumulation of intermediates that may be able to crosslink to native tissue and to provide an increase in collagen crosslinking to foster tissue regeneration in vivo.…”

Section: Discussionmentioning

confidence: 99%

Non‐enzymatic glycation of chondrocyte‐seeded collagen gels for cartilage tissue engineering

Roy¹,

Boskey²,

Bonassar³

2008

Journal Orthopaedic Research

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Collagen glycated with ribose (250 mM) in solution (pre-glycation) and as a gel (post-glycation) was seeded with chondrocytes and the effects of glycation on chondrocyte matrix assembly in culture were determined. Pre-glycation enhanced GAG accumulation significantly over controls at both 2 and 4 weeks (p < 0.05), although at both time points there were no statistical differences in cell number between pre-glycated and control gels. The increased proteoglycan accumulation was shown to be in part due to significantly increased GAG retention by the pre-glycated constructs (p < 0.05). Total collagen content in these pre-glycated gels was also significantly higher than unglycated gels at 4 weeks (p < 0.05). With post-glycation of collagen gels, chondrocyte number and GAG accumulation were all significantly lower than controls (p < 0.05). Post-glycation also inhibited GAG retention by the constructs (p < 0.05). Given these results, pre-glycation may be an improved processing method for collagen gels for tissue engineering techniques. ß

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“…BAPN treated explants also display markedly inhibited functional integrative cartilage repair in vitro (43). Cartilage explants pretreated with BAPN, followed by its withdrawal before a period of integrative repair resulted in an ultimate increase in integrative strength of the explant (44). The authors suggest that BAPN pre-treatment resulted in an accumulation of "primed" collagen molecules containing unmodified hydroxylysine residues that were, upon BAPN withdrawal, rapidly oxidized by LOX or a lysyl oxidase isoform(s) (44,45).…”

Section: Volume 286 • Number 2 • January 14 2011mentioning

confidence: 99%

“…Cartilage explants pretreated with BAPN, followed by its withdrawal before a period of integrative repair resulted in an ultimate increase in integrative strength of the explant (44). The authors suggest that BAPN pre-treatment resulted in an accumulation of "primed" collagen molecules containing unmodified hydroxylysine residues that were, upon BAPN withdrawal, rapidly oxidized by LOX or a lysyl oxidase isoform(s) (44,45). Taken together, these studies emphasize that collagen cross-linking and organization resulting from lysyl oxidase activity is required for the correct generation and maintenance of a cartilage-containing extracellular matrix.…”

Section: Volume 286 • Number 2 • January 14 2011mentioning

confidence: 99%

Lysyl Oxidase-like-2 (LOXL2) Is a Major Isoform in Chondrocytes and Is Critically Required for Differentiation

Iftikhar¹,

Hurtado²,

Bais

et al. 2011

Journal of Biological Chemistry

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The lysyl oxidase family is made up of five members: lysyl oxidase (LOX) and lysyl oxidase-like 1-4 (LOXL1-LOXL4). All members share conserved C-terminal catalytic domains that provide for lysyl oxidase or lysyl oxidase-like enzyme activity; and more divergent propeptide regions. LOX family enzyme activities catalyze the final enzymatic conversion required for the formation of normal biosynthetic collagen and elastin cross-links. The importance of lysyl oxidase enzyme activity to normal bone development has long been appreciated, but regulation and roles for specific LOX isoforms in bone formation in vivo is largely unexplored. Fracture healing recapitulates aspects of endochondral bone development. The present study first investigated the expression of all LOX isoforms in fracture healing. A remarkable coincidence of LOXL2 expression with the chondrogenic phase of fracture healing was found, prompting more detailed analyses of LOXL2 expression in normal growth plates, and LOXL2 expression and function in developing ATDC5 chondrogenic cells. Data show that LOXL2 is expressed by pre-hypertrophic and hypertrophic chondrocytes in vivo, and that LOXL2 expression is regulated in vitro as a function of chondrocyte differentiation. Moreover, LOXL2 knockdown studies in vitro show that LOXL2 expression is required for ATDC5 chondrocyte cell line differentiation through regulation of SNAIL and SOX9, important transcription factors that control chondrocyte differentiation. Taken together, data provide evidence that LOXL2, like LOX, is a multifunctional protein. LOXL2 promotes chondrocyte differentiation by mechanisms that are likely to include roles as both a regulator and an effector of chondrocyte differentiation.The lysyl oxidase family is made up of five members: lysyl oxidase (LOX) 3 and lysyl oxidase-like 1-4 (LOXL1-LOXL4)(1). All five members share a conserved C-terminal catalytic domain that provides for lysyl oxidase or lysyl oxidase-like enzyme activity, and more divergent propeptide regions. LOX family enzyme activities catalyze the final enzymatic conversion required for the subsequent formation of normal lysinederived biosynthetic cross-links found in collagens and elastin (2). The importance of lysyl oxidase enzyme activity to normal bone development has long been known, and is based in part on studies in which enzyme activities are inhibited by lathyrogens in vivo (3), including ␤-aminopropionitrile, a potent inhibitor of LOX and LOX isoform activity (4). The LOX family can be subdivided into two subgroups. Although all members have similarities in the catalytic C-terminal region, LOX and LOXL1 are more closely related to each other than they are to LOXL2-LOXL4. Moreover, the pro-peptide regions of LOX and LOXL1 have very little similarity to each other and no similarity to LOXL2-LOXL4. The pro-regions of LOXL2-LOXL4 each contain four scavenger receptor cysteine-rich (SRCR) domains whose functions are likely to depend on interactions with other proteins (1). The pro-regions of all LOX family members may have...

show abstract

Treatment of cartilage with β-aminopropionitrile accelerates subsequent collagen maturation and modulates integrative repair

Cited by 23 publications

References 33 publications

High fidelity visualization of cell-to-cell variation and temporal dynamics in nascent extracellular matrix formation

High fidelity visualization of cell-to-cell variation and temporal dynamics in nascent extracellular matrix formation

Non‐enzymatic glycation of chondrocyte‐seeded collagen gels for cartilage tissue engineering

Lysyl Oxidase-like-2 (LOXL2) Is a Major Isoform in Chondrocytes and Is Critically Required for Differentiation

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