Ultrastructural immunolocalization of cartilage oligomeric matrix protein (COMP) in relation to collagen fibrils in the equine tendon

Södersten, Fredrik; Ekman, Stina; Eloranta, Maija‐Leena; Heinegård, Dick; Dudhia, Jayesh; Hultenby, Kjell

doi:10.1016/j.matbio.2005.06.003

Cited by 58 publications

(59 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, patients with PSACH or MED and mice expressing mutant COMP exhibit thicker collagen fibrils in tendon and ligaments (59). Further, high levels of COMP in equine tendon correlated with thinner collagen fibrils (60). This agrees well with the distribution of COMP in human skin, where it is mainly localized in the papillary dermis, which is characterized by collagen fibrils of smaller diameter.…”

Section: Discussionsupporting

confidence: 69%

Collagen XII and XIV, New Partners of Cartilage Oligomeric Matrix Protein in the Skin Extracellular Matrix Suprastructure

Agarwal

Zwolanek

Keene

et al. 2012

Journal of Biological Chemistry

124

View full text Add to dashboard Cite

Background:What is the biological function of COMP in skin ECM? Results: COMP binds collagens XII and XIV that associate with collagen I fibrils. All three proteins localize to anchoring plaques. Conclusion: COMP acts as an adapter in ECM of healthy skin, organizing the dermal collagen network. Significance: COMP organizes collagen I fibrils into a suprastructure that may contribute to stabilizing cohesion between the upper dermis and the basement membrane zone.

show abstract

Section: Discussionsupporting

confidence: 69%

Collagen XII and XIV, New Partners of Cartilage Oligomeric Matrix Protein in the Skin Extracellular Matrix Suprastructure

Agarwal

Zwolanek

Keene

et al. 2012

Journal of Biological Chemistry

124

View full text Add to dashboard Cite

show abstract

“…Sections were rinsed in buffer and fixed in 2% glutaraldehyde, contrasted with 0.1% uranyl acetate, embedded in 2% methylcellulose, and examined in a Tecnai 10 (FEI Company, The Netherlands) at 80 kV. Images were taken using a Megaview III digital camera (38).…”

Section: Isolation Of Rat Liver Mitochondriamentioning

confidence: 99%

The amyloid β-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae

Petersen

Alikhani²,

Behbahani³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

619

453

View full text Add to dashboard Cite

The amyloid ␤-peptide (A␤) has been suggested to exert its toxicity intracellularly. Mitochondrial functions can be negatively affected by A␤ and accumulation of A␤ has been detected in mitochondria. Because A␤ is not likely to be produced locally in mitochondria, we decided to investigate the mechanisms for mitochondrial A␤ uptake. Our results from rat mitochondria show that A␤ is transported into mitochondria via the translocase of the outer membrane (TOM) machinery. The import was insensitive to valinomycin, indicating that it is independent of the mitochondrial membrane potential. Subfractionation studies following the import experiments revealed A␤ association with the inner membrane fraction, and immunoelectron microscopy after import showed localization of A␤ to mitochondrial cristae. A similar distribution pattern of A␤ in mitochondria was shown by immunoelectron microscopy in human cortical brain biopsies obtained from living subjects with normal pressure hydrocephalus. Thus, we present a unique import mechanism for A␤ in mitochondria and demonstrate both in vitro and in vivo that A␤ is located to the mitochondrial cristae. Importantly, we also show that extracellulary applied A␤ can be internalized by human neuroblastoma cells and can colocalize with mitochondrial markers. Together, these results provide further insight into the mitochondrial uptake of A␤, a peptide considered to be of major significance in Alzheimer's disease.Alzheimer disease ͉ protein import ͉ human brain biopsies T he amyloid-␤ peptide (A␤) is produced by regulated intramembrane proteolysis of the A␤ precursor protein (APP) by the sequential cleavage by ␤-and ␥-secretases (1-2). Plaques consisting mainly of aggregated A␤ are detected in the neuropil in aged subjects and in particular in subjects with Alzheimer's disease (AD) (3-5). Recently, it has been argued that it is A␤ oligomers and fibrils that cause toxicity, loss of synapses, and ultimately neuronal death (6-9). The exact mechanisms of how A␤ damages the neurons are still unknown; however, several lines of evidence implicate that A␤ exerts its toxicity intracellularly (10, 11) and point toward a role of mitochondria in this process (12). It has been reported that mitochondrial A␤ accumulation impairs neuronal function and, thus, contributes to cellular dysfunction in a transgenic APP mouse model (13). It is noteworthy that in AD at an early stage there is already a reduction in the number of mitochondria (14), the brain glucose metabolism is decreased (15), and the activities of both tricarboxylic acid cycle enzymes (16) and cytochrome c oxidase (COX) are reduced (17)(18)(19)(20). In vitro studies with isolated mitochondria suggest that A␤ 1-42 inhibits COX activity in a copper-dependent manner (21). Furthermore, mitochondrial A␤-binding alcohol dehydrogenase (ABAD) has been found to be up-regulated in neurons from AD patients (22), and A␤ has been shown to interact with ABAD, resulting in free radical production and neuronal apoptosis. Recently, we have shown that preseque...

show abstract

“…RNA was assessed by spectrophotometry at 260:280 nm and by 1% agarose gel electrophoresis. RNA was used for quantitative RT/PCR of collagen types I and III, 22,24 IGF-I, 25 and cartilage oligomeric matrix protein (COMP), [26][27][28] as indicators of tendon matrix synthesis, and matrix metalloproteinase-3 (MMP-3), [29][30][31] matrix metalloproteinase-13 (MMP-13), 24,29,32 and aggrecanase (ADAMTS-4) 30,33 as indicators of tendon catabolism.…”

Section: Rna Isolation and Quantitative Rt/pcrmentioning

confidence: 99%

Mesenchymal stem cells and insulin‐like growth factor‐I gene‐enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons

Schnabel

Lynch

Meulen

et al. 2009

Journal Orthopaedic Research

225

206

View full text Add to dashboard Cite

Tendinitis remains a catastrophic injury among athletes. Mesenchymal stem cells (MSCs) have recently been investigated for use in the treatment of tendinitis. Previous work has demonstrated the value of insulin-like growth factor-I (IGF-I) to stimulate cellular proliferation and tendon fiber deposition in the core lesion of tendinitis. This study examined the effects of MSCs, as well as IGF-I geneenhanced MSCs (AdIGF-MSCs) on tendon healing in vivo. Collagenase-induced bilateral tendinitis lesions were created in equine flexor digitorum superficialis tendons (SDFT). Tendons were treated with 10 Â 10 6 MSCs or 10 Â 10 6 AdIGF-MSCs. Control limbs were injected with 1 mL of phosphate-buffered saline (PBS). Ultrasound examinations were performed at t ¼ 0, 2, 4, 6, and 8 weeks. Horses were euthanized at 8 weeks and SDFTs were mechanically tested to failure and evaluated for biochemical composition and histologic characteristics. Expression of collagen types I and III, IGF-I, cartilage oligomeric matrix protein (COMP), matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13), and aggrecanase-1 (ADAMTS-4) were similar in MSC and control tendons. Both MSC and AdIGF-MSC injection resulted in significantly improved tendon histological scores. These findings indicate a benefit to the use of MSCs and AdIGF-MSCs for the treatment of tendinitis. ß

show abstract

Ultrastructural immunolocalization of cartilage oligomeric matrix protein (COMP) in relation to collagen fibrils in the equine tendon

Cited by 58 publications

References 36 publications

Collagen XII and XIV, New Partners of Cartilage Oligomeric Matrix Protein in the Skin Extracellular Matrix Suprastructure

Collagen XII and XIV, New Partners of Cartilage Oligomeric Matrix Protein in the Skin Extracellular Matrix Suprastructure

The amyloid β-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae

Mesenchymal stem cells and insulin‐like growth factor‐I gene‐enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons

Contact Info

Product

Resources

About