title: Targeted overexpression of vitamin D receptor in osteoblasts increases calcium concentration without affecting structural properties of bone mineral crystals.
abstract: Increased cross-sectional area and strength of long bones has been observed in transgenic mice with 2-fold (OSV9) and 3-fold (OSV3) elevation of osteoblast vitamin D receptor (VDR) levels. In the present study, mineralization density distributions, including typical calcium content (Ca(Peak)) and homogeneity of mineralization (Ca(Width)) of femoral bone and growth plate cartilage, were determined by quantitative backscattered electron imaging (qBEI). Fourier-transform infrared (FTIR) microspectroscopy was used to examine mineral content, collagen and crystal maturation, and scanning small angle X-ray scattering (scanning-SAXS) for studying mineral particle thickness and alignment. In addition, X-ray diffraction (XRD) of distal tibiae revealed mineral particle c-axis size. In trabecular bone, the increase in Ca(Peak) was significant for both OSV9 (+ 3.14%, P = 0.03) and OSV3 (+ 3.43%, P = 0.02) versus controls with 23.61 +/- 0.45 S.D. wt% Ca baseline values. In cortical bone, Ca(Peak) was enhanced for the OSV3 mice (+ 1.84%, P = 0.02) versus controls with 26.61 +/- 0.28 S.D. wt% Ca, and OSV9 having intermediate values. Additionally, there was significantly increased homogeneity of mineralization as denoted by a reduction of Ca(Width) (-8.4%, P = 0.01) in primary spongiosa. FTIR microspectroscopy, with the exception of an increased collagen maturity in OSV3 trabecular bone (+ 9.9%, P = 0.02), XRD, and scanning-SAXS indicated no alterations in the nanostructure of transgenic bone. These findings indicate that elevation of osteoblastic vitamin D response led to formation of normal bone with higher calcium content. These material properties, together with indications of decreased bone resorption in secondary spongiosa and increased cortical periosteal bone formation, appear to contribute to the improved mechanical properties of their long bones and suggest an important physiological role of the vitamin D-endocrine system in normal bone mineralization.
authors.affiliation: Ludwig Boltzmann Institute of Osteology, 4th Med. Dept, Hanusch Hospital & UKH Meidling, Vienna, Austria.
authors.forename: B M
authors.initials: BM
authors.lastname: Misof
authors.forename: P
authors.initials: P
authors.lastname: Roschger
authors.forename: W
authors.initials: W
authors.lastname: Tesch
authors.forename: P A
authors.initials: PA
authors.lastname: Baldock
authors.forename: A
authors.initials: A
authors.lastname: Valenta
authors.forename: P
authors.initials: P
authors.lastname: Messmer
authors.forename: J A
authors.initials: JA
authors.lastname: Eisman
authors.forename: A L
authors.initials: AL
authors.lastname: Boskey
authors.forename: E M
authors.initials: EM
authors.lastname: Gardiner
authors.forename: P
authors.initials: P
authors.lastname: Fratzl
authors.forename: K
authors.initials: K
authors.lastname: Klaushofer
mesh_terms: D000818:Animals; D015519:Bone Density; D002118:Calcium / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism / Q000648:ultrastructure; D003460:Crystallization; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000378:metabolism* / Q000648:ultrastructure; D015870:Gene Expression; D018390:Gene Targeting; D006132:Growth Plate / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning / Q000379:methods; D010006:Osteoblasts / Q000378:metabolism* / Q000648:ultrastructure; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D012542:Scattering, Radiation; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D018167:Receptors, Calcitriol; D002118:Calcium