CCN2/CTGF binds the small leucine rich proteoglycan protein Tsukushi

Ohta, Kunimasa; Aoyama, Eriko; Ahmad, Saboor; Ito, Naofumi; Anam, Mohammad Badrul; Kubota, Satoshi; Takigawa, Masaharu

doi:10.1007/s12079-018-0487-x

Cited by 17 publications

(21 citation statements)

References 33 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CTGF (encoding for CTGF/CCN2) is active in chondrocytes and plays important roles in wound healing and fibrotic processes [ 35 ]. Under normal conditions, the regulation of terminal chondrocyte differentiation by CTGF/CCN2 is opposed by tsukushi, a member of the SLRP group, that affects proliferating and hypertrophic zones of the growth plate [ 36 ]. Underexpression of TSK , gene for tsukushi, might thus contribute to the presence of not well organized and differentiated cartilage islands in DSLD tendons [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis

et al. 2020

View full text Add to dashboard Cite

Background Equine degenerative suspensory ligament desmitis (DSLD) is a systemic connective tissue disorder first identified in Peruvian Paso horses but afflicting other horse breeds as well. Inappropriate accumulation of proteoglycans in connective tissues, most prominently in tendons and ligaments, leads to progressive and debilitating lameness and pain. It is largely unknown what drives the overproduction of proteoglycans, but our previous studies suggest involvement of bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor-β (TGFβ) family, impacting synthesis of proteoglycans. To identify potential players in pathogenesis of DSLD a new approach utilizing next generation sequencing was undertaken. Methods Next generation sequencing was performed using RNA extracted from skin biopsies of six control Peruvian Pasos and six horses with DSLD (4 Peruvian Pasos and 2 warmbloods). The CuffDiff result sets were validated with algorithms used to run them. This was based on the determined false discovery rates derived from the P values adjusted for multiple testing for any given result. Results Bioinformatics analysis of transcriptomes revealed differential expression of over 1500 genes, including increased expression of genes for several growth factors (most prominently BMP2, FGF5, CTGF, many members of the EGF family), and mediators of signaling (Fos, Myc, MAPK system), and keratins. Two genes encoding for enzymes involved in synthesis of hyaluronan were also overexpressed. Gene expression was decreased for protein cores of many proteoglycans, several growth factors, most collagens, and many peptides with immune function. Conclusions The overexpression of BMP2 correlates well with our previous data. However, the decrease in expression of numerous proteoglycans was unexpected. A mutation in a gene of a less characterized proteoglycan and/or glycosyltransferase with subsequent increased production of hyaluronan and/or a proteoglycan(s) undetected in our study could account for the systemic proteoglycan deposition. Decreased collagen gene expression indicates abnormal connective tissue metabolism. The increased expression of keratin genes and FGF5 supports reports of skin abnormalities in DSLD. Underexpression of immune function genes corresponds with lack of inflammation in DSLD tissues. Finally, though the proteoglycan and/or glycosaminoglycan abundant in DSLD has not been identified, we validated our previous data, including overexpression of BMP2, and systemic nature of DSLD due to disturbed metabolism of the extracellular matrix.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…CTGF (encoding for CTGF/CCN2) is active in chondrocytes, and plays important roles in wound healing and brotic processes (35). Under normal conditions the regulation of terminal chondrocyte differentiation by CTGF/CCN2 is opposed by tsukushi, a member of the SLRP group, that affects proliferating and hypertrophic zones of the growth plate (36). Underexpression of TSK, gene for tsukushi, might thus contribute to the presence of not well organized and differentiated cartilage islands in DSLD tendons (1).…”

Section: Discussionmentioning

confidence: 99%

Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis

Haythorn¹,

Young²,

Stanton³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Equine Degenerative Suspensory Desmitis (DSLD) is a systemic connective tissue disorder first identified in Peruvian Paso horses, but afflicting other horse breeds as well. Inappropriate accumulation of proteoglycans in connective tissues, most prominently in tendons and ligaments leads to progressive and debilitating lameness and pain. It is largely unknown what drives the overproduction of proteoglycans, but our previous studies suggest involvement of bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor β (TGFβ) family, impacting synthesis of proteoglycans. To identify potential players in pathogenesis of DSLD a new approach utilizing next generation sequencing was undertaken. Methods Next generation sequencing was performed using RNA extracted from skin biopsies of six control Peruvian Pasos and six horses with DSLD (4 Peruvian Pasos and 2 Warmbloods). The CuffDiff result sets were validated with algorithms used to run them. This was based on the determined False Discovery Rates derived from the P-values adjusted for multiple testing for any given result. Results Bioinformatics analysis of transcriptomes revealed differential expression of over 1500 genes, including increased expression of genes for several growth factors (most prominently BMP2, FGF5, CTGF, members of the EGF family), of mediators of signaling (Fos, Myc, MAPK system), and keratins. Two genes encoding for enzymes involved in synthesis of hyaluronan were also overexpressed. Gene expression was decreased for protein cores of many proteoglycans, several growth factors, most collagens and many peptides with immune function. Conclusions The overexpression of BMP2 correlates well with our previous data. However, the decrease in expression of numerous proteoglycans was unexpected. A mutation in a gene of a less characterized proteoglycan and/or glycosyltransferase with subsequent increased production of hyaluronan and/or a proteoglycan(s) undetected in our study could account for the systemic proteoglycan deposition. Decreased collagen gene expression indicates abnormal connective tissue metabolism. The increased expression of keratin genes and FGF5 supports reports of skin abnormalities in DSLD. Underexpression of immune function genes corresponds with lack of inflammation in DSLD tissues. Finally, though the proteoglycan and/or glycosaminoglycan abundant in DSLD has not been identified, we validated our previous data, including overexpression of BMP2 , and systemic nature of DSLD due to disturbed metabolism of the extracellular matrix.

show abstract

“…CTGF (encoding for CTGF/CCN2) is active in chondrocytes, and plays important roles in wound healing and brotic processes (29). Under normal conditions the regulation of terminal chondrocyte differentiation by CTGF/CCN2 is opposed by tsukushi, a member of the SLRP group, that affects proliferating and hypertrophic zones of the growth plate (30). Underexpression of TSK, gene for tsukushi, might thus contribute to the presence of not well organized and differentiated cartilage islands in DSLD tendons (1).…”

Section: Discussionmentioning

confidence: 99%

Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis

Haythorn¹,

Young²,

Stanton³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Equine Degenerative Suspensory Desmitis (DSLD) is a systemic connective tissue disorder first identified in Peruvian Paso horses, but afflicting other horse breeds as well. Inappropriate accumulation of proteoglycans in connective tissues, most prominently in tendons and ligaments leads to lameness and pain. It is largely unknown what drives the overproduction of proteoglycans, but our previous data suggest involvement of bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor β (TGFβ) family, impacting synthesis of proteoglycans. To identify potential players in pathogenesis of DSLD a new approach utilizing next generation sequencing was undertaken. Methods Next generation sequencing was performed using RNA extracted from skin biopsies of six control Peruvian Pasos and six horses with DSLD (4 Peruvian Pasos and 2 Warmbloods). The CuffDiff result sets were validated with algorithms used to run them. This was based on the determined False Discovery Rates derived from the P-values adjusted for multiple testing for any given result. Results Bioinformatics analysis of transcriptomes revealed differential expression of over 1500 genes, including increased expression of genes for several growth factors (BMP2, FGF5, CTGF, members of the EGF family), of mediators of signaling (Fos, Myc, MAPK system), and keratins. Two genes encoding for enzymes involved in synthesis of hyaluronan were overexpressed. Gene expression was decreased for protein cores of many proteoglycans, several growth factors, most collagens and many peptides with immune function. Conclusions The overexpression of BMP2 correlates well with our previous data. However, the decrease in expression of numerous proteoglycans was unexpected. A mutation in a gene of a less characterized proteoglycan and/or glycosyltransferase with subsequent increased production of hyaluronan and/or a proteoglycan(s) undetected in our study could account for the systemic proteoglycan deposition. Decreased collagen gene expression indicates abnormal connective tissue metabolism. The increased expression of keratin genes and FGF5 supports reports of skin abnormalities in DSLD. Underexpression of immune function genes corresponds with lack of inflammation in DSLD tissues. Finally, though the proteoglycan and/or glycosaminoglycan abundant in DSLD has not been identified, we validated our previous data, including overexpression of BMP2, and systemic nature of DSLD due to disturbed metabolism of the extracellular matrix.

show abstract

CCN2/CTGF binds the small leucine rich proteoglycan protein Tsukushi

Cited by 17 publications

References 33 publications

Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis

Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis

Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis

Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis

Contact Info

Product

Resources

About