Functional Roles of the Tissue Inhibitor of Metalloproteinase 3 (TIMP-3) during Ascorbate-induced Differentiation of Osteoblastic MC3T3-E1 Cells

Suzuki, Hironao; Nezaki, Yuko; Kuno, Eriko; Sugiyama, Ikuko; Mizutani, Akifumi; Tsukagoshi, Norihiro

doi:10.1271/bbb.67.1737

Cited by 14 publications

(8 citation statements)

References 28 publications

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“…The expression of MMPs and TIMPs examined in this study was all highest in proliferative stage in culture without IL-1a as well as previous reports using osteoblasts (Kusano et al, 1998;Suzuki et al, 2003;Manduca et al, 2005). The levels of MMP-1, -2, -3, -13, and -14 expressed in cultures with IL-1a exceeded the levels in the control through day 14 of culture, increasing markedly from the proliferative to the later stages of culture.…”

Section: Discussionsupporting

confidence: 87%

The effect of IL-1α on the expression of matrix metalloproteinases, plasminogen activators, and their inhibitors in osteoblastic ROS 17/2.8 cells

et al. 2006

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Section: Discussionsupporting

confidence: 87%

The effect of IL-1α on the expression of matrix metalloproteinases, plasminogen activators, and their inhibitors in osteoblastic ROS 17/2.8 cells

et al. 2006

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“…This is supported by a number of previous [ 55 – 63 ] and more recent studies [ 32 , 34 , 64 , 65 ] challenging current dogma, showing that hypertrophic chondrocytes can transdifferentiate into osteoblasts during endochondral bone formation. This may lead to continued expression of collagen type II and consequently Timp-3 , resulting in inhibition of osteoblast differentiation [ 66 ]. Our data revealing no changes in endosteal osteoblast number or osteocyte lacunar occupancy in either Timp-3 KO or Tg mouse tibial cortices suggest that any cells making such hypertrophic chondrocyte-to-osteoblast transition do not confer changes in osteoblast behaviour.…”

Section: Discussionmentioning

confidence: 99%

Deficiency and Also Transgenic Overexpression of Timp-3 Both Lead to Compromised Bone Mass and Architecture In Vivo

et al. 2016

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Tissue inhibitor of metalloproteinases-3 (TIMP-3) regulates extracellular matrix via its inhibition of matrix metalloproteinases and membrane-bound sheddases. Timp-3 is expressed at multiple sites of extensive tissue remodelling. This extends to bone where its role, however, remains largely unresolved. In this study, we have used Micro-CT to assess bone mass and architecture, histological and histochemical evaluation to characterise the skeletal phenotype of Timp-3 KO mice and have complemented this by also examining similar indices in mice harbouring a Timp-3 transgene driven via a Col-2a-driven promoter to specifically target overexpression to chondrocytes. Our data show that Timp-3 deficiency compromises tibial bone mass and structure in both cortical and trabecular compartments, with corresponding increases in osteoclasts. Transgenic overexpression also generates defects in tibial structure predominantly in the cortical bone along the entire shaft without significant increases in osteoclasts. These alterations in cortical mass significantly compromise predicted tibial load-bearing resistance to torsion in both genotypes. Neither Timp-3 KO nor transgenic mouse growth plates are significantly affected. The impact of Timp-3 deficiency and of transgenic overexpression extends to produce modification in craniofacial bones of both endochondral and intramembranous origins. These data indicate that the levels of Timp-3 are crucial in the attainment of functionally-appropriate bone mass and architecture and that this arises from chondrogenic and osteogenic lineages.

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“…One previous study reported TIMP-3 is expressed in osteoblasts, and that its expression is up-regulated during differentiation of MC3T3-E1 cells. In addition, the expression of osteocalcia, osteonectin, and osteopontin are all inhibited by overexpression of TIMP-3 [ 22 ]. Hence, MMP-3 and TIMP-3 are important mediators for osteoblast function.…”

Section: Introductionmentioning

confidence: 99%

Association betweenMMP3andTIMP3polymorphisms and risk of osteoarthritis

et al. 2017

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Osteoarthritis (OA) is the most commonly occurring degenerative joint disease worldwide, and its incidence has increased in recent years. We evaluated whether there is the association between MMP-3 and TIMP-3 variants and susceptibility to OA in a Chinese population. Venous blood samples were collected from 431 female participants (200 cases and 231 controls) at Hong Hui Hospital, Xi’an Jiaotong University College of Medicine between 2015 and 2016. After genotyping the samples using standard protocols, the association between MMP-3 and TIMP-3 single nucleotide polymorphisms and risk of OA was assessed by calculating odds ratios (ORs) and 95% confidence intervals (95% CIs) using unconditional logistic regression analysis. The minor G allele of rs650108 was associated with OA risk in a recessive model (p = 0.034, OR = 1.82, 95%CI = 1.04-3.18), while the minor A allele of rs715572 was associated with OA risk in a recessive model (p = 0.030, OR = 1.88, 95%CI = 1.05-3.34). Thus a suggestive association was observed in a discovery case-control study between OA and two common SNPs, rs650108 in MMP-3 and rs715572 in TIMP-3.

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Functional Roles of the Tissue Inhibitor of Metalloproteinase 3 (TIMP-3) during Ascorbate-induced Differentiation of Osteoblastic MC3T3-E1 Cells

Cited by 14 publications

References 28 publications

The effect of IL-1α on the expression of matrix metalloproteinases, plasminogen activators, and their inhibitors in osteoblastic ROS 17/2.8 cells

The effect of IL-1α on the expression of matrix metalloproteinases, plasminogen activators, and their inhibitors in osteoblastic ROS 17/2.8 cells

Deficiency and Also Transgenic Overexpression of Timp-3 Both Lead to Compromised Bone Mass and Architecture In Vivo

Association betweenMMP3andTIMP3polymorphisms and risk of osteoarthritis

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