Substrate Strain Mitigates Effects of β-Aminopropionitrile-Induced Reduction in Enzymatic Crosslinking

Canelón, Silvia P.; Wallace, Joseph M.

doi:10.1007/s00223-019-00603-3

“…This study was designed to block collagen cross-linking in skeletal muscle. BAPN has been previously shown to be an effective collagen cross-linking inhibitor in multiple tissues [ 23 , 52 ] and similar effects in muscle were anticipated. The dosage of 100 mg/kg/day and intraperitoneal delivery method were similar to previous experiments showing effectiveness of BAPN in blocking collagen cross-linking [ 28 , 53 ].…”

Section: Discussionmentioning

confidence: 69%

Collagen cross-links scale with passive stiffness in dystrophic mouse muscles, but are not altered with administration of a lysyl oxidase inhibitor

Brashear

¹

,

Wohlgemuth²,

Hu³

et al. 2022

View full text Add to dashboard Cite

In Duchenne muscular dystrophy (DMD), a lack of functional dystrophin leads to myofiber instability and progressive muscle damage that results in fibrosis. While fibrosis is primarily characterized by an accumulation of extracellular matrix (ECM) components, there are changes in ECM architecture during fibrosis that relate more closely to functional muscle stiffness. One of these architectural changes in dystrophic muscle is collagen cross-linking, which has been shown to increase the passive muscle stiffness in models of fibrosis including the mdx mouse, a model of DMD. We tested whether the intraperitoneal injections of beta-aminopropionitrile (BAPN), an inhibitor of the cross-linking enzyme lysyl oxidase, would reduce collagen cross-linking and passive stiffness in young and adult mdx mice compared to saline-injected controls. We found no significant differences between BAPN treated and saline treated mice in collagen cross-linking and stiffness parameters. However, we observed that while collagen cross-linking and passive stiffness scaled positively in dystrophic muscles, collagen fiber alignment scaled with passive stiffness distinctly between muscles. We also observed that the dystrophic diaphragm showed the most dramatic fibrosis in terms of collagen content, cross-linking, and stiffness. Overall, we show that while BAPN was not effective at reducing collagen cross-linking, the positive association between collagen cross-linking and stiffness in dystrophic muscles still show cross-linking as a viable target for reducing passive muscle stiffness in DMD or other fibrotic muscle conditions.

show abstract

“…Briefly, periostin serves as a scaffold for BMP-1 and collagen in order to promote collagen cross-linking. BMP-1 cleaves the inactive form of LOX to generate the active form, which catalyzes the covalent cross-linking of collagen molecules [ 111 , 112 ]. Periostin-null mice exhibited abnormal collagen fibrillogenesis in the periosteum and a decrease in collagen cross-linking in the skin, tendons, and heart [ 11 ].…”

Section: Functionmentioning

confidence: 99%

Periostin: biology and function in cancer

Dorafshan

¹

,

Razmi

²

,

Safaei

³

et al. 2022

View full text Add to dashboard Cite

Periostin (POSTN), a member of the matricellular protein family, is a secreted adhesion-related protein produced in the periosteum and periodontal ligaments. Matricellular proteins are a nonstructural family of extracellular matrix (ECM) proteins that regulate a wide range of biological processes in both normal and pathological conditions. Recent studies have demonstrated the key roles of these ECM proteins in the tumor microenvironment. Furthermore, periostin is an essential regulator of bone and tooth formation and maintenance, as well as cardiac development. Also, periostin interacts with multiple cell-surface receptors, especially integrins, and triggers signals that promote tumor growth. According to recent studies, these signals are implicated in cancer cell survival, epithelial-mesenchymal transition (EMT), invasion, and metastasis. In this review, we will summarize the most current data regarding periostin, its structure and isoforms, expressions, functions, and regulation in normal and cancerous tissues. Emphasis is placed on its association with cancer progression, and also future potential for periostin-targeted therapeutic approaches will be explored.

show abstract

“…This study was designed to block collagen cross-linking in skeletal muscle. BAPN has been previously shown to be an effective collagen cross-linking inhibitor in multiple tissues (23, 52) and similar effects in muscle were anticipated. The dosage of 100 mg/kg/day and intraperitoneal delivery method were similar to previous experiments showing effectiveness of BAPN in blocking collagen cross-linking (53, 54).…”

Section: Discussionmentioning

confidence: 57%

Collagen content and cross-links scale with passive stiffness in dystrophic mouse muscles, but are not altered with administration of collagen cross-linking inhibitor beta-aminopropionitrile

Brashear¹,

Wohlgemuth²,

Hu³

et al. 2022

Preprint

1

0

View full text Add to dashboard Cite

In Duchenne muscular dystrophy (DMD), a lack of functional dystrophin leads to myofiber instability and progressive muscle damage that results in fibrosis. While fibrosis is primarily characterized by an accumulation of extracellular matrix (ECM) components, there are changes in ECM architecture during fibrosis that relate more closely to functional muscle stiffness. One of these architectural changes in dystrophic muscle is collagen cross-linking, which has been shown to increase the passive muscle stiffness in models of fibrosis including the mdx mouse, a model of DMD. We tested whether the intraperitoneal injections of beta-aminopropionitrile (BAPN), an inhibitor of the cross-linking enzyme lysyl oxidase, would reduce collagen cross-linking and passive stiffness in young and adult mdx mice compared to saline-injected controls. We found no significant differences between BAPN treated and saline treated mice in collagen cross-linking and stiffness parameters. However, we observed that while collagen cross-linking and passive stiffness scaled positively in dystrophic muscles, collagen fiber alignment scaled with passive stiffness distinctly between muscles. We also observed that the dystrophic diaphragm showed the most dramatic fibrosis in terms of collagen content, cross-linking, and stiffness. Overall, we show that while BAPN was not effective at reducing collagen cross-linking, the positive association between collagen cross-linking and stiffness in dystrophic muscles still show cross-linking as a viable target for reducing passive muscle stiffness in DMD or other fibrotic muscle conditions.

show abstract

Substrate Strain Mitigates Effects of β-Aminopropionitrile-Induced Reduction in Enzymatic Crosslinking

Cited by 9 publications

References 32 publications

Collagen cross-links scale with passive stiffness in dystrophic mouse muscles, but are not altered with administration of a lysyl oxidase inhibitor

Collagen cross-links scale with passive stiffness in dystrophic mouse muscles, but are not altered with administration of a lysyl oxidase inhibitor

Periostin: biology and function in cancer

Collagen content and cross-links scale with passive stiffness in dystrophic mouse muscles, but are not altered with administration of collagen cross-linking inhibitor beta-aminopropionitrile

Contact Info

Product

Resources

About