Remodeling of extracellular matrices initiates and advances calcification during development and healing of bones and teeth

Sasano, Yasuyuki; Nakamura, Megumi; Okata, Hiroshi; Henmi, Akiko; Mikami, Yasuto

doi:10.1016/j.job.2011.06.001

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…The periodontal ligament in the tooth of mammals has similar structure of the hinge ligament of bivalves. Similar function of human MMPs has been reported in human bones and teeth (Sasano et al, 2012). MMPs degrade extracellular matrices which inhibit the growth of hydroxyapatite to make some space and hydroxyapatite crystals can then be formed in this space.…”

Section: Introductionsupporting

confidence: 67%

Functional Analyses of MMPs for Aragonite Crystal Formation in the Ligament of Pinctada fucata

et al. 2018

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The mollusk class, Bivalvia, plays an important role in the formation of calcium carbonate in the ocean. The bivalve hinge ligament is a hard but pliant tissue that resists the stress placed on the hinge during opening and closing. The ligament comprises a fine microstructure of fibrous aragonite crystals surrounded by a dense organic matrix. The matrix consists of organic fibers that are aligned with the fibrous aragonite crystals. Previous studies identified a tissue inhibitor of metalloproteinase (Pf-TIMP: Pinctada fucata-Tissue Inhibitor of Metalloproteinase) in the organic fibers of P. fucata ligaments. This enzyme exhibited strong inhibition of matrix metalloproteinase (MMP) activity in vitro, suggesting that MMPs also play a role in formation of the organic fibers of the ligament. Using transcriptome data, we identified MMP genes from the mantle isthmus, which is a soft tissue attached to the ligament. To investigate the function of MMP genes in vivo, we performed RNA interference experiments. The expression of MMP14973 and MMP07860 genes was inhibited after injection of each dsRNA. Cumulative injection of MMP07860 dsRNA induced aggregated aragonite fiber orientation, whereas the injection of MMP14973 showed minor effects. When the decalcified ligament was incubated in a solution saturated with calcium carbonate, aragonite fibers aligned along the surface. When the decalcified ligament was treated with recombinant human (hr) MMP-13, the precipitation of calcium carbonate was inhibited. To investigate general MMP functions in calcium carbonate crystallization in detail, we precipitated aragonite crystals in collagen gels treated with or without recombinant human (hr) MMP-1. Treatment with hrMMP-1 increased the interaction between collagen gels and calcium carbonate. These results imply that Pinctada fucata (Pf)-MMPs degrade extracellular matrices in the ligament to produce the fine organic fibers that regulate the orientation of fibrous aragonite crystals.

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Section: Introductionsupporting

confidence: 67%

Functional Analyses of MMPs for Aragonite Crystal Formation in the Ligament of Pinctada fucata

et al. 2018

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“…It has been reported that MMP‐2‐deficient mice display osteoporosis and progressive loss of BMD in long bones (Inoue et al , ; Mosig et al , ). MMPs may be involved in calcification in bone development (Sasano et al , ). Our previous study showed that osteoblasts and osteocytes express MMPs 2, 8 and 13 as well as bone matrix proteins such as type I collagen and osteocalcin during bone healing in rat calvarial defects (Itagaki et al , ).…”

Section: Discussionmentioning

confidence: 99%

“…Embryonic and postembryonic bone development exhibits characteristic extracellular events, such as accumulation of extracellular matrix molecules (Sasano et al, 2000a,b;Zhu et al, 2001;Gorski et al, 2004;Midura et al, 2004Midura et al, , 2007, increase in and maturation of mineral crystals (Legros et al, 1987;Tarnowski et al, 2002;Ferguson et al, 2003;Akkus et al, 2004;Busa et al, 2005;Miller et al, 2007;Donnelly et al, 2010;Kimura et al, 2011) and degradation of extracellular matrix molecules (Dean et al, 1992;Hoshi et al, 1999Hoshi et al, , 2001Sasano et al, 2002Sasano et al, , 2012Nakamura et al, 2005;Sakuraba et al, 2006;Golub, 2009). Little information is available about such extracellular events and their roles during bone healing.…”

Section: Introductionmentioning

confidence: 99%

Calcification during bone healing in a standardised rat calvarial defect assessed by micro‐CTandSEM‐EDX

et al. 2014

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Bone matrix calcification during embryonic and postembryonic rat calvarial development assessed by SEM–EDX spectroscopy, XRD, and FTIR spectroscopy

et al. 2015

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Bone mineral is constituted of biological hydroxyapatite crystals. In developing bone, the mineral crystal matures and the Ca/P ratio increases. However, how an increase in the Ca/P ratio is involved in maturation of the crystal is not known. The relationships among organic components and mineral changes are also unclear. The study was designed to investigate the process of calcification during rat calvarial bone development. Calcification was evaluated by analyzing the atomic distribution and concentration of Ca, P, and C with scanning electron microscopy (SEM)-energy-dispersive X-ray (EDX) spectroscopy and changes in the crystal structure with X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Histological analysis showed that rat calvarial bone formation started around embryonic day 16. The areas of Ca and P expanded, matching the region of the developing bone matrix, whereas the area of C became localized around bone. X-ray diffraction and FTIR analysis showed that the amorphous-like structure of the minerals at embryonic day 16 gradually transformed into poorly crystalline hydroxyapatite, whereas the proportion of mineral to protein increased until postnatal week 6. FTIR analysis also showed that crystallization of hydroxyapatite started around embryonic day 20, by which time SEM-EDX spectroscopy showed that the Ca/P ratio had increased and the C/Ca and C/P ratios had decreased significantly. The study suggests that the Ca/P molar ratio increases and the proportion of organic components such as proteins of the bone matrix decreases during the early stage of calcification, whereas crystal maturation continues throughout embryonic and postembryonic bone development.

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Remodeling of extracellular matrices initiates and advances calcification during development and healing of bones and teeth

Cited by 6 publications

References 37 publications

Functional Analyses of MMPs for Aragonite Crystal Formation in the Ligament of Pinctada fucata

Functional Analyses of MMPs for Aragonite Crystal Formation in the Ligament of Pinctada fucata

Calcification during bone healing in a standardised rat calvarial defect assessed by micro‐CTandSEM‐EDX

Bone matrix calcification during embryonic and postembryonic rat calvarial development assessed by SEM–EDX spectroscopy, XRD, and FTIR spectroscopy

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