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Abcc6 null mice a model mineralization disorder PXE show vertebral osteopenia without enhanced intervertebral disc calcification with aging

ABSTRACT: Transcriptomic analysis of annulus fibrosus (AF) tissues from intervertebral discs of 7-month-old mice with the global deletion of ABCC6. ABCC6 is an efflux transporter of ATP in hepatic cells and loss of function results in metabolic ectopic mineralization disorder pseudoxanthoma elsaticum. To understand the role of ABCC6 and ectopic mineralization in the disc, we examined the transcriptomic profiles of annulus fibrosus cells in control and ABCC6 knock-out mice using microarrays.

ORGANISM(S): Mus musculus

PROVIDER: GSE188943 | GEO | 2021/11/17

REPOSITORIES: GEO

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Loss of function mutation in progressive ankylosis (Ank) gene causes aberrant mineralization and acquisition of osteoblast-like-phenotype by annulus fibrosus cells in the intervertebral disc

Project description:Transcriptomic analysis of nucleus pulposus (NP) and annulus fibrosus (AF) tissues from intervertebral discs of 3-month-old mice with loss of function mutation of Ank gene. Regulator of extracellular inorganic pyrophosphate, Ank is essential for preventing ectopic mineralization in the extracellular matrices, maintaining the health of the intervertebral disc of mice. We examined the transcriptomic profiles of nucleus pulposus and annulus fibrosus cells in control and Ank mutant mice using microarrays.

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Abcc6 null mice a model mineralization disorder PXE show vertebral osteopenia without enhanced intervertebral disc calcification with aging

Project description:Abcc6 null mice a model mineralization disorder PXE show vertebral osteopenia without enhanced intervertebral disc calcification with aging

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<i>Abcc6</i> Null Mice-a Model for Mineralization Disorder PXE Shows Vertebral Osteopenia Without Enhanced Intervertebral Disc Calcification With Aging.

Project description:Chronic low back pain is a highly prevalent health condition intricately linked to intervertebral disc degeneration. One of the prominent features of disc degeneration that is commonly observed with aging is dystrophic calcification. ATP-binding cassette sub-family C member 6 (ABCC6), a presumed ATP efflux transporter, is a key regulator of systemic levels of the mineralization inhibitor pyrophosphate (PPi). Mutations in ABCC6 result in pseudoxanthoma elasticum (PXE), a progressive human metabolic disorder characterized by mineralization of the skin and elastic tissues. The implications of ABCC6 loss-of-function on pathological mineralization of structures in the spine, however, are unknown. Using the Abcc6 -/- mouse model of PXE, we investigated age-dependent changes in the vertebral bone and intervertebral disc. Abcc6 -/- mice exhibited diminished trabecular bone quality parameters at 7 months, which remained significantly lower than the wild-type mice at 18 months of age. Abcc6 -/- vertebrae showed increased TRAP staining along with decreased TNAP staining, suggesting an enhanced bone resorption as well as decreased bone formation. Surprisingly, however, loss of ABCC6 resulted only in a mild, aging disc phenotype without evidence of dystrophic mineralization. Finally, we tested the utility of oral K3Citrate to treat the vertebral phenotype since it is shown to regulate hydroxyapatite mechanical behavior. The treatment resulted in inhibition of the osteoclastic response and an early improvement in mechanical properties of the bone underscoring the promise of potassium citrate as a therapeutic agent. Our data suggest that although ectopic mineralization is tightly regulated in the disc, loss of ABCC6 compromises vertebral bone quality and dysregulates osteoblast-osteoclast coupling.

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