Identification of the membrane-type matrix metalloproteinase MT1-MMP in osteoclasts

Sato, Takashi; Ovejero, Maria del Carmen; Peng, Hou; Heegaard, Anne‐Marie; Kumegawa, Masayoshi; Foged, Niels T.; Delaissé, Jean‐Marie

doi:10.1242/jcs.110.5.589

Cited by 191 publications

(7 citation statements)

References 41 publications

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“… 147 MT1-MMP-knockout (KO) mice usually die couple of months after birth, and display a severe phenotype that includes delayed ossification, unclosed sutures and unremoved cartilage. 148 MMP-14 is highly expressed on osteoclast podosomes, 149 and it digests interstitial collagen as well as other ECM molecules. 150 MMP-9-KO mice showed reduced osteoclast invasion into the core of developing bones, 151 and in vitro, osteoclasts lacking MMP9 did not migrate.…”

Section: Osteoclastsmentioning

confidence: 99%

Bone remodeling: an operational process ensuring survival and bone mechanical competence

2022

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Bone remodeling replaces old and damaged bone with new bone through a sequence of cellular events occurring on the same surface without any change in bone shape. It was initially thought that the basic multicellular unit (BMU) responsible for bone remodeling consists of osteoclasts and osteoblasts functioning through a hierarchical sequence of events organized into distinct stages. However, recent discoveries have indicated that all bone cells participate in BMU formation by interacting both simultaneously and at different differentiation stages with their progenitors, other cells, and bone matrix constituents. Therefore, bone remodeling is currently considered a physiological outcome of continuous cellular operational processes optimized to confer a survival advantage. Bone remodeling defines the primary activities that BMUs need to perform to renew successfully bone structural units. Hence, this review summarizes the current understanding of bone remodeling and future research directions with the aim of providing a clinically relevant biological background with which to identify targets for therapeutic strategies in osteoporosis.

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Section: Osteoclastsmentioning

confidence: 99%

Bone remodeling: an operational process ensuring survival and bone mechanical competence

2022

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“…Cells form different membrane protrusions to explore the surrounding ECM, such as filopodia [ 284 ] and lamellipodia [ 285 ]. MMP-14 has been reported to be also localized to filopodia [ 286 ] and lamellipodia, where it indirectly associates with the actin cytoskeleton by binding with its HPX domain to the hyaluronan receptor CD44 [ 287 , 288 , 289 , 290 ]. These membrane protrusions are mechanically stabilized by adhesive matrix contacts, to which several adhesome components are recruited, e.g., regulators of lamellipodial cell migration, Rac, WASp, Arp2/3, arpin, lamellipodin, WAVE, Mena, and Ena/VASP family members.…”

Section: Cellular Adhesome Structures In the Tmementioning

confidence: 99%

Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression

Niland

Riscanevo

Eble

2021

IJMS

194

107

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Cancer progression with uncontrolled tumor growth, local invasion, and metastasis depends largely on the proteolytic activity of numerous matrix metalloproteinases (MMPs), which affect tissue integrity, immune cell recruitment, and tissue turnover by degrading extracellular matrix (ECM) components and by releasing matrikines, cell surface-bound cytokines, growth factors, or their receptors. Among the MMPs, MMP-14 is the driving force behind extracellular matrix and tissue destruction during cancer invasion and metastasis. MMP-14 also influences both intercellular as well as cell–matrix communication by regulating the activity of many plasma membrane-anchored and extracellular proteins. Cancer cells and other cells of the tumor stroma, embedded in a common extracellular matrix, interact with their matrix by means of various adhesive structures, of which particularly invadopodia are capable to remodel the matrix through spatially and temporally finely tuned proteolysis. As a deeper understanding of the underlying functional mechanisms is beneficial for the development of new prognostic and predictive markers and for targeted therapies, this review examined the current knowledge of the interplay of the various MMPs in the cancer context on the protein, subcellular, and cellular level with a focus on MMP14.

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“…Rac1 augments dimer formation of MT1-MMP and proMMP-2 activation at lamellipodia Using the chimera construct, we next investigated whether there are any factors that might regulate the dimer formation of MT1-MMP on the cell surface. Since it has been reported that MT1-MMP is localized at the lamellipodia structure in walking osteoclasts (Sato et al, 1997), we looked at the effect of a constitutively active form of the small GTPase Rac1 (V12Rac1, Rac1DA) on dimer formation as a GTP-bound form of Rac1 stimulates the generation of lamellipodia in cells (Michiels et al, 1995). MT1-F/NGFR was co-expressed with Rac1DA in COS1 cells and the phosphotyrosine signal was monitored.…”

Section: Mt1-mmp Forms a Homophilic Complex On The Cell Surfacementioning

confidence: 99%

Homophilic complex formation of MT1-MMP facilitates proMMP-2 activation on the cell surface and promotes tumor cell invasion

Itoh¹,

Takamura²,

Ito³

et al. 2001

The EMBO Journal

366

379

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Activation of proMMP‐2 by MT1‐MMP is considered to be a critical event in cancer cell invasion. In the activation step, TIMP‐2 bound to MT1‐MMP on the cell surface acts as a receptor for proMMP‐2. Subsequently, adjacent TIMP‐2‐free MT1‐MMP activates the proMMP‐2 in the ternary complex. In this study, we demonstrate that MT1‐MMP forms a homophilic complex through the hemopexin‐like (PEX) domain that acts as a mechanism to keep MT1‐MMP molecules close together to facilitate proMMP‐2 activation. Deletion of the PEX domain in MT1‐MMP, or swapping the domain with the one derived from MT4‐MMP, abolished the ability to activate proMMP‐2 on the cell surface without affecting the proteolytic activities. In addition, expression of the mutant MT1‐MMP lacking the catalytic domain (MT1PEX‐F) efficiently inhibited complex formation of the full‐length enzymes and activation of pro MMP‐2. Furthermore, expression of MT1PEX‐F inhibited proMMP‐2 activation and Matrigel invasion activity of invasive human fibrosarcoma HT1080 cells. These findings elucidate a new function of the PEX domain: regulating MT1‐MMP activity on the cell surface, which accelerates cellular invasiveness in the tissue.

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Identification of the membrane-type matrix metalloproteinase MT1-MMP in osteoclasts

Cited by 191 publications

References 41 publications

Bone remodeling: an operational process ensuring survival and bone mechanical competence

Bone remodeling: an operational process ensuring survival and bone mechanical competence

Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression

Homophilic complex formation of MT1-MMP facilitates proMMP-2 activation on the cell surface and promotes tumor cell invasion

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