Multiple Roles of the SO42−/Cl−/OH− Exchanger Protein Slc26a2 in Chondrocyte Functions

Park, Meeyoung; Ohana, Ehud; Choi, Soo Young; Lee, Myeong‐Sok; Park, Jong Hoon; Muallem, Shmuel

doi:10.1074/jbc.m113.503466

Cited by 32 publications

(27 citation statements)

References 41 publications

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“…DTDST is an essential SO 4 2− transporter expressed prominently in chondrocytes [53, 61, 62], and mutations of this gene have been associated with a number of inherited chondrodysplasias [62–66]. There is also abundant DTDST mRNA in the small and large intestine of mice, rats and humans [46, 53, 61, 63, 67, 68].…”

Section: The Pathways and Mechanisms For Oxalate Transport Across Thementioning

confidence: 99%

The role of intestinal oxalate transport in hyperoxaluria and the formation of kidney stones in animals and man

Whittamore

Hatch

2016

Urolithiasis

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The intestine exerts a considerable influence over urinary oxalate in two ways, through the absorption of dietary oxalate and by serving as an adaptive extra-renal pathway for elimination of this waste metabolite. Knowledge of the mechanisms responsible for oxalate absorption and secretion by the intestine therefore have significant implications for understanding the etiology of hyperoxaluria, as well as offering potential targets for future treatment strategies for calcium oxalate kidney stone disease. In this review, we present the recent developments and advances in this area over the past 10 years, and put to the test some of the new ideas that have emerged during this time, using human and mouse models. A key focus for our discussion are the membrane-bound anion exchangers, belonging to the SLC26 gene family, some of which have been shown to participate in transcellular oxalate absorption and secretion. This has offered the opportunity to not only examine the roles of these specific transporters, revealing their importance to oxalate homeostasis, but to also probe the relative contributions made by the active transcellular and passive paracellular components of oxalate transport across the intestine. We also discuss some of the various physiological stimuli and signaling pathways which have been suggested to participate in the adaptation and regulation of intestinal oxalate transport. Finally, we offer an update on research into Oxalobacter formigenes, alongside recent investigations of other oxalate-degrading gut bacteria, in both laboratory animals and humans.

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Section: The Pathways and Mechanisms For Oxalate Transport Across Thementioning

confidence: 99%

The role of intestinal oxalate transport in hyperoxaluria and the formation of kidney stones in animals and man

Whittamore

Hatch

2016

Urolithiasis

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“…It likely indicative of a low level of differentiation of chondrocytes because PAX1 is expressed at the early stages of sclerotome chondrogenic differentiation 42. The IHH gene is the principle transcription factor that is involved in the recognition of activating signals from both Bmp and IGF and is normally expressed in prehypertrophic chondrocytes of the growth plate 43. We discovered single hypertrophic cells on the concave sides of growth plates of IS patients, and a high level of expression of this gene suggests a trend towards chondrocyte hypertrophy in patients with IS.…”

Section: Resultsmentioning

confidence: 99%

A New Look at Causal Factors of Idiopathic Scoliosis: Altered Expression of Genes Controlling Chondroitin Sulfate Sulfation and Corresponding Changes in Protein Synthesis in Vertebral Body Growth Plates

et al. 2019

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Background: In a previous report, we demonstrated the presence of cells with a neural/glial phenotype on the concave side of the vertebral body growth plate in Idiopathic Scoliosis (IS) and proposed this phenotype alteration as the main etiological factor of IS. In the present study, we utilized the same specimens of vertebral body growth plates removed during surgery for Grade III-IV IS to analyse gene expression. We suggested that phenotype changes observed on the concave side of the vertebral body growth plate can be associated with altered expression of particular genes, which in turn compromise mechanical properties of the concave side.Methods: We used a Real-Time SYBR Green PCR assay to investigate gene expression in vertebral body growth plates removed during surgery for Grade III-IV IS; cartilage tissues from human fetal spine were used as a surrogate control. Special attention was given to genes responsible for growth regulation, chondrocyte differentiation, matrix synthesis, sulfation and transmembrane transport of sulfates. We performed morphological, histochemical, biochemical, and ultrastructural analysis of vertebral body growth plates.Results: Expression of genes that control chondroitin sulfate sulfation and corresponding protein synthesis was significantly lower in scoliotic specimens compared to controls. Biochemical analysis showed 1) a decrease in diffused proteoglycans in the total pool of proteoglycans; 2) a reduced level of their sulfation; 3) a reduction in the amount of chondroitin sulfate coinciding with raising the amount of keratan sulfate; and 4) reduced levels of sulfation on the concave side of the scoliotic deformity.Conclusion: The results suggested that altered expression of genes that control chondroitin sulfate sulfation and corresponding changes in protein synthesis on the concave side of vertebral body growth plates could be causal agents of the scoliotic deformity.

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“…SLC26A2 , a diastrophic dysplasia sulphate transporter gene, encodes a transmembrane protein that transports sulphate into chondrocytes to maintain adequate proteoglycan sulphation [ 12 , 33 ]. As bicarbonate can be transported across cell plasma membranes by anion exchangers of the SLC26 gene families, and the main constituent part of otoliths is dense calcium carbonate crystals.…”

Section: Discussionmentioning

confidence: 99%

“…In this way, it modifies inner ear acid-base homeostasis [ 40 ]. Slc26a2 is an SO4 2- /Cl - /OH - exchanger [ 12 ]. It is here speculated that slc26a2 contributes to the ionic endolymph environment and creates an osmotic gradient to establish the ion potential in developing hair cells.…”

Section: Discussionmentioning

confidence: 99%

“…SLC26A2 is a diastrophic dysplasia sulphate transporter necessary for proteoglycan synthesis in the bone and cartilage extracellular matrix and for expansion of chondrocyte volume [ 10 – 11 ]. SLC26A2 has been reported to be a SO4 2- /Cl - /OH - exchanger and it is precisely regulated by extracellular Cl - [ 12 ]. Mutations in four human SLC26 genes have been found to be associated with congenital and early-onset Mendelian diseases: chondrodysplasias ( SLC26A2 ), chloride diarrhea ( SLC26A3 ), and deafness with enlargement of the vestibular aqueduct ( SLC26A4 ) [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Solute Carrier Family 26 Member a2 (slc26a2) Regulates Otic Development and Hair Cell Survival in Zebrafish

Liu

Xia

et al. 2015

PLoS ONE

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Hearing loss is one of the most prevalent human birth defects. Genetic factors contribute to the pathogenesis of deafness. It is estimated that one-third of deafness genes have already been identified. The current work is an attempt to find novel genes relevant to hearing loss using guilt-by-profiling and guilt-by-association bioinformatics analyses of approximately 80 known non-syndromic hereditary hearing loss (NSHL) genes. Among the 300 newly identified candidate deafness genes, slc26a2 were selected for functional studies in zebrafish. The slc26a2 gene was knocked down using an antisense morpholino (MO), and significant defects were observed in otolith patterns, semicircular canal morphology, and lateral neuromast distributions in morphants. Loss-of-function defects are caused primarily by apoptosis, and morphants are insensitive to sound stimulation and imbalanced swimming behaviours. Morphant defects were found to be partially rescued by co-injection of human SLC26A2 mRNA. All the results suggest that bioinformatics is capable of predicting new deafness genes and this showed slc26a2 is to be a critical otic gene whose dysfunction may induce hearing impairment.

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Multiple Roles of the SO42−/Cl−/OH− Exchanger Protein Slc26a2 in Chondrocyte Functions

Cited by 32 publications

References 41 publications

The role of intestinal oxalate transport in hyperoxaluria and the formation of kidney stones in animals and man

The role of intestinal oxalate transport in hyperoxaluria and the formation of kidney stones in animals and man

A New Look at Causal Factors of Idiopathic Scoliosis: Altered Expression of Genes Controlling Chondroitin Sulfate Sulfation and Corresponding Changes in Protein Synthesis in Vertebral Body Growth Plates

Solute Carrier Family 26 Member a2 (slc26a2) Regulates Otic Development and Hair Cell Survival in Zebrafish

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