title: Expression of osteogenic molecules in the caudate nucleus and gray matter and their potential relevance for Basal Ganglia calcification in hypoparathyroidism.
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.
authors.affiliation: Departments of Endocrinology and Metabolism (R.G., S.M., M.D., M.K., N.T., S.S.), Forensic Medicine (T.M.), Anatomy (T.S.R.), and Biostatistics (V.S.), All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Goswami
authors.forename: Tabin
authors.initials: T
authors.lastname: Millo
authors.forename: Shruti
authors.initials: S
authors.lastname: Mishra
authors.forename: Madhuchhanda
authors.initials: M
authors.lastname: Das
authors.forename: Mansi
authors.initials: M
authors.lastname: Kapoor
authors.forename: Neeraj
authors.initials: N
authors.lastname: Tomar
authors.forename: Soma
authors.initials: S
authors.lastname: Saha
authors.forename: Tara Shankar
authors.initials: TS
authors.lastname: Roy
authors.forename: Vishnubhatla
authors.initials: V
authors.lastname: Sreenivas
mesh_terms: D001480:Basal Ganglia Diseases / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002114:Calcinosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D002421:Caudate Nucleus / Q000378:metabolism* / Q000473:pathology; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D006801:Humans; D007011:Hypoparathyroidism / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism* / Q000473:pathology; D015675:Osteocalcin / Q000378:metabolism; D015676:Osteonectin / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D050659:Core Binding Factor Alpha 1 Subunit; D015676:Osteonectin; C493709:RUNX2 protein, human; D044168:Receptor, Parathyroid Hormone, Type 1; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D015675:Osteocalcin; D053495:Osteopontin