Expression of osteogenic molecules in the caudate nucleus and gray matter and their potential relevance for Basal Ganglia calcification in hypoparathyroidism

J Clin Endocrinol Metab. 2014 May;99(5):1741-8. doi: 10.1210/jc.2013-3863. Epub 2014 Feb 19.

Abstract

Background: Basal ganglia calcification (BGC) is an interesting example of ectopic calcification in patients with hypoparathyroidism. Its pathogenesis and reasons for predilection of calcification at basal ganglia are not clear.

Objective: To assess the expression of osteogenesis-related molecules in the caudate nucleus and surface gray matter (an area spared from calcification) and discuss potential relevance of the results in context of BGC in idiopathic hypoparathyroidism.

Methods: Caudate nucleus and gray matter were obtained from 14 autopsies performed in accidental deaths. The mRNA expression of bone transcription factors (RUNX2/osterix), bone morphogenetic proteins (BMPs) 2 and 4, osteonectin, osteopontin, osteocalcin, vitamin D receptor, calcium sensing-receptor, Na phosphate transporters (PiTs) 1 and 2, N-methyl-D-aspartate receptor 2B (NMDAR2B), carbonic anhydrase II (CA-II), PTH1 receptor (PTH1R), PTH2R, and PTHrP were assessed by RT-PCR. Western blot, spot densitometry, and immunohistochemistry were performed to assess protein expression of molecules showing differences in mRNA expression between caudate and gray tissues.

Results: The mean mRNA expression of PiT1 (11.0 ± 10.39 vs 32.9 ± 20.98, P = .003) and PTH2R (1.6 ± 1.47 vs 13.7 ± 6.11, P = .001) were significantly lower in the caudate nucleus than the gray matter. The expression of osteonectin, osteopontin, and CA-II were significantly higher in the caudate nucleus than the gray matter (P = .01, .001, and .04, respectively). The mRNA expression of other molecules was comparable in the 2 tissues. The protein expression of both CA-II and osteonectin was 24% higher and PiT1 17% lower in caudate than the gray matter. The differences in the PTH2R and osteopontin protein expression were not appreciable.

Conclusions: The presence of several osteogenic molecules in caudate nucleus indicates that BGC would probably be the outcome of an active process. The differences in expression of these molecules in caudate over gray matter could favor BGC at this site in the unique biochemical milieu of hypoparathyroid state.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Basal Ganglia Diseases / complications
  • Basal Ganglia Diseases / metabolism*
  • Basal Ganglia Diseases / pathology
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Morphogenetic Protein 4 / metabolism
  • Calcinosis / complications
  • Calcinosis / metabolism*
  • Calcinosis / pathology
  • Caudate Nucleus / metabolism*
  • Caudate Nucleus / pathology
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Humans
  • Hypoparathyroidism / complications
  • Hypoparathyroidism / metabolism*
  • Hypoparathyroidism / pathology
  • Nerve Fibers, Unmyelinated / metabolism*
  • Nerve Fibers, Unmyelinated / pathology
  • Osteocalcin / metabolism
  • Osteonectin / metabolism
  • Osteopontin / metabolism
  • Receptor, Parathyroid Hormone, Type 1 / metabolism
  • Receptors, Calcitriol / metabolism
  • Receptors, Calcium-Sensing / metabolism

Substances

  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Core Binding Factor Alpha 1 Subunit
  • Osteonectin
  • RUNX2 protein, human
  • Receptor, Parathyroid Hormone, Type 1
  • Receptors, Calcitriol
  • Receptors, Calcium-Sensing
  • Osteocalcin
  • Osteopontin