Redundant function of the heparan sulfate 6‐O‐endosulfatases Sulf1 and Sulf2 during skeletal development

Ratzka, Andreas; Kalus, Ina; Moser, Markus; Dierks, Thomas; Mundlos, Stefan; Vortkamp, Andrea

doi:10.1002/dvdy.21423

Cited by 80 publications

(86 citation statements)

References 41 publications

(68 reference statements)

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“…Nevertheless, both SULF1 and SULF2 expression was detected in a sub-population of articular chondrocytes. Unlike increasing expression of SULF1/SULF2 with age reported by Ratzka et al (Ratzka et al 2008), we found the levels of these enzymes in adult human as well as rodent articular cartilage to be much lower than that observed during fetal development. The in vivo expression, however, was in marked contrast to the prolonged in vitro differentiation of chondrocytic cell line ATDC5 showing an increase in Sulf1 but a decrease in Sulf2.…”

Section: Discussioncontrasting

confidence: 99%

“…Our studies show that cartilage and bone cells do not follow this trend but instead retain an easily detectable level of both SULF1 and SULF2 expression in postnatal and adult skeletal elements that also agrees with previous studies demonstrating some Sulf1/Sulf2 expression in fetal and postnatal tissues (Zhao et al 2006;Otsuki et al 2008;Ratzka et al 2008). Previously, only adult neuronal tissues have been found to express high levels of these enzymes (Joy et al 2015); some low level expression in endothelial cells has been documented where they have been shown to act as cell signalling inhibitors (Sahota and Dhoot 2009).…”

Section: Discussionsupporting

confidence: 93%

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Expression of Sulf1 and Sulf2 in cartilage, bone and endochondral fracture healing

Zaman

Staines

Farquharson

et al. 2015

Histochem Cell Biol

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Highlights: High Sulf1/Sulf2 expression in active osteoblasts with reduction in osteocytes. High variability in Sulf1/Sulf2 expression in articular chondrocytes. Hypertrophic chondrocytes in growing and healing bone express high levels of Sulf2 but not Sulf1. High Sulf2 expression in growing and healing bone closely correlates with Hedgehog signalling.ABSTRACT: SULF1/SULF2 enzymes regulate cell signalling that impacts the growth and differentiation of many tissues. To determine their possible role in cartilage and bone growth or repair, their expression was examined during development and bone fracture healing using RT-PCR and immunochemical analyses. Examination of epiphyseal growth plates revealed differential, inverse patterns of SULF1 and SULF2 expression, with the former enriched in quiescent and the latter in hypertrophic chondrocyte zones. Markedly higher levels of both SULFs, however, were expressed in osteoblasts actively forming bone when compared with proliferating pre-osteoblasts in the periosteum or the entombed osteocytes which express the lowest levels. The increased Sulf1 and Sulf2 expression in differentiating osteoblasts was further confirmed by RT PCR analysis of mRNA levels in rat calvarial osteoblast cultures.SULF1 and SULF2 were expressed in most fetal articular chondrocytes but downregulated in a larger subset of cells in the postnatal articular cartilage. Unlike adult articular chondrocytes, SULF1/SULF2 expression varied markedly in postnatal hypertrophic chondrocytes in the growth plate, with very high SULF2 expression compared with SULF1 apparent during neonatal growth in both primary and secondary centres of ossification. Similarly, hypertrophic chondrocytes expressed greatly higher levels of SULF2 but not SULF1 during bone fracture healing. SULF2 expression unlike SULF1 also spread to the calcifying matrix around the hypertrophic chondrocytes indicating its possible ligand inhibiting role through HSPG desulfation. Higher levels of SULF2 in both developing and healing bone closely correlated with parallel increases in hedgehog signalling analysed by ptc1 receptor expression.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 93%

Expression of Sulf1 and Sulf2 in cartilage, bone and endochondral fracture healing

Zaman

Staines

Farquharson

et al. 2015

Histochem Cell Biol

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“…However, double knockout mice exhibit reduced body mass and die shortly after birth suggesting functional redundancy amongst the sulf family (Lamanna et al, 2006;Holst et al, 2007). This is consistent with the reported overlapping expression profiles of SULF enzymes during mouse embryonic development (Lum et al, 2007;Ratzka et al, 2008). The various phenotypes of Sulf double knockout mice and Xenopus morphants reflect the dynamic regulation of Sulf enzymes in a spatial and temporal manner.…”

Section: Introductionsupporting

confidence: 82%

“…Like the mammalian Sulf homologs, sulf1 is the major source of Sulf in the eye and olfactory epithelium. Mouse Sulfs are also abundantly expressed in cartilage and bone (Ratzka et al, 2008). Although these structures develop after 2.5dpf, we were able to detect sulf1 and sulf2 expression at 60hpf in the pharyngeal arches and pectoral finbuds, which eventually will form the jaw skeleton and the girdle cartilages (Kimmel et al, 1995).…”

Section: Comparison Of Hs Sulf1 Expression From Various Speciesmentioning

confidence: 70%

“…Although many studies have shown Sulfs affect many signalling molecules, sulf1 or sulf2 single knockout mice show no striking phenotype in overall development, with mild defects reported in bone formation, lung and eosphageal innervation (Ai et al, 2007;Lum et al, 2007;Ratzka et al, 2008). However, double knockout mice exhibit reduced body mass and die shortly after birth suggesting functional redundancy amongst the sulf family (Lamanna et al, 2006;Holst et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Dynamic expression patterns of 6‐O endosulfatases during zebrafish development suggest a subfunctionalisation event for sulf2

Gorsi

Whelan

2010

Developmental Dynamics

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The 6-O-endosulfatase enzymes (Sulfs) edit the final sulfation pattern and function of heparan sulfate (HS) by removal of 6-O-sulfate groups from the chain. To date, two mammalian sulf genes have been identified that regulate many signalling pathways during embryonic development. In zebrafish a sulf1 ortholog and duplicate copies of the mammalian sulf2 gene, sulf2a and sulf2, have been identified, which contain conserved motifs characteristic of vertebrate sulf genes. Zebrafish sulf1 and sulf2a are broadly expressed in the central nervous system (CNS) and non-neuronal tissue including heart, somite boundaries, olfactory system, and otic vesicle, whereas sulf2 expression is almost entirely restricted to the CNS. The duplicate copies of sulf2 have distinct expression patterns, which together mirror that of mouse sulf2, suggesting duplication in the teleost lineage has been followed by subfunctionalisation, whereby both genes need to be preserved by selection to ensure the ancestral gene's expression profile and function is maintained. Developmental Dynamics 239:3312-3323,

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Mass Spectrometry in Carbohydrate Sequencing and Binding Analysis

Staples

Zaia

2011

Carbohydrate Recognition

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Redundant function of the heparan sulfate 6‐O‐endosulfatases Sulf1 and Sulf2 during skeletal development

Cited by 80 publications

References 41 publications

Expression of Sulf1 and Sulf2 in cartilage, bone and endochondral fracture healing

Expression of Sulf1 and Sulf2 in cartilage, bone and endochondral fracture healing

Dynamic expression patterns of 6‐O endosulfatases during zebrafish development suggest a subfunctionalisation event for sulf2

Mass Spectrometry in Carbohydrate Sequencing and Binding Analysis

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