Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

Vos, Ivo J. H. M. de; Wong, Arnette Shi Wei; Welting, T.; Coull, Barry J.; Steensel, Maurice A. M. Van

doi:10.1002/ajmg.a.61264

Cited by 22 publications

(30 citation statements)

References 93 publications

(301 reference statements)

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“…For instance, over half of the members of the MMP family are involved in promoting bone growth and development under normal physiological conditions, 6 and mutations in the human MMP2 and MMP14 genes have been linked to rare skeletal diseases characterized by loss of bone tissue and short stature. 7 MMPs are produced by a wide variety of cell types (eg, stromal fibroblasts, macrophages, and endothelial and epithelial cells) and are expressed as inactive zymogens (proenzymes) containing a propeptide domain that must be removed for protease activity. 2,4,8 In vertebrates, there are at least 28 different MMPs, and at least 23 of them are expressed in humans.…”

Section: Overview Of the Role Of Mmps In Health And Diseasementioning

confidence: 99%

Matrix Metalloproteinases and Glaucoma Treatment

Weinreb

Robinson

Dibas

et al. 2020

Journal of Ocular Pharmacology and Therapeutics

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Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade extracellular matrix (ECM) components such as collagen and have important roles in multiple biological processes, including development and tissue remodeling, both in health and disease. The activity of MMPs is influenced by the expression of MMPs and tissue inhibitors of metalloproteinase (TIMPs). In the eye, MMP-mediated ECM turnover in the juxtacanalicular region of the trabecular meshwork (TM) reduces outflow resistance in the conventional outflow pathway and helps maintain intraocular pressure (IOP) homeostasis. An imbalance in the MMP/TIMP ratio may be involved in the elevated IOP often associated with glaucoma. The prostaglandin analog/prostamide (PGA) class of topical ocular hypotensive medications used in glaucoma treatment reduces IOP by increasing outflow through both conventional and unconventional (uveoscleral) outflow pathways. Evidence from in vivo and in vitro studies using animal models and anterior segment explant and cell cultures indicates that the mechanism of IOP lowering by PGAs involves increased MMP expression in the TM and ciliary body, leading to tissue remodeling that enhances conventional and unconventional outflow. PGA effects on MMP expression are dependent on the identity and concentration of the PGA. An intracameral sustained-release PGA implant (Bimatoprost SR) in development for glaucoma treatment can reduce IOP for many months after expected intraocular drug bioavailability. We hypothesize that the higher concentrations of bimatoprost achieved in ocular outflow tissues with the implant produce greater MMP upregulation and more extensive, sustained MMP-mediated target tissue remodeling, providing an extended duration of effect. IOP, intraocular pressure; MMP, matrix metalloproteinase; MT-MMP, membrane-type MMP; TIMP, tissue inhibitor of metalloproteinase.MMPS AND GLAUCOMA TREATMENT 209 210 WEINREB ET AL.

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Section: Overview Of the Role Of Mmps In Health And Diseasementioning

confidence: 99%

Matrix Metalloproteinases and Glaucoma Treatment

Weinreb

Robinson

Dibas

et al. 2020

Journal of Ocular Pharmacology and Therapeutics

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“…This enzyme can be activated extracellularly and intracellularly and is involved in multiple pathways. Mutations in this gene are associated with the Winchester syndrome [34]. Recent studies have indicated that MMP2 is highly expressed in many tumors, and its increase promotes proliferation and metastasis, and reduces tumor cell apoptosis [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

MMP1 and MMP9 are potential prognostic biomarkers and targets for uveal melanoma

Wang

Zhang

Bai

et al. 2021

Preprint

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Background: Uveal melanoma (UVM) is the leading cause of eye-related mortality worldwide. This study aimed to explore the expression and prognostic value of matrix metalloproteinases (MMPs) in UVM.Methods: Gene expression levels were obtained from the Gene Expression Omnibus (GEO) and Oncomine databases. Functional and pathway enrichment analyses were performed using the Metascape database. GeneMANIA was then applied to construct a protein-protein interaction network and identify the hub genes. Moreover, overall (OS) and disease-free survival (DFS) analysis for the hub genes was performed using the UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) online tool. Furthermore, TRRUST was used to predict the targets of the MMPs. Results: Our results revealed that the transcriptional levels of MMP1, MMP9, MMP10, MMP11, MMP13, MMP14, and MMP17 were upregulated in UVM tissues compared to normal tissues. A protein-protein interaction (PPI) network was constructed, and the top 50 hub genes were identified. The functions of MMPs and their neighboring proteins are mainly associated with ECM-receptor interaction, proteoglycans in cancer, the IL-17 signaling pathway, and microRNAs in cancer. Among the MMPs, MMP1/2/9/11/14/15/16/17/24 played significant roles in the progression of UVM from stage 3 to stage 4. We also found that the expression of MMP1, MMP 2, MMP 9, and MMP 16 was positively correlated with OS and DFS in patients with UVM. Additionally, 18 transcription factors associated with nine MMPs were identified.Conclusions: The results of this study may provide potential biomarkers and targets for UVM. However, further studies are required to confirm these results.

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“…In general, most children with MMP2 mutations are apparently healthy at birth, but signs of skeletal deformities begin from six months to eleven years old. Thereafter, features of arthropathy gradually appear, including joint pain, joint contracture and swelling of distal extremities, and other symptoms then progressively develop, such as coarse facies and gum hypertrophy (36). Vanatka et al (37) reported a case of MONA with long-term follow-up, in which the pathological changes of the bones over a 23-year period were striking and the pattern of bone loss was progressive and periarticular.…”

Section: Mmp2 In Hereditary Skeletal Dysplasiamentioning

confidence: 99%

Different roles of matrix metalloproteinase 2 in osteolysis of skeletal dysplasia and bone metastasis (Review)

Jin

Tan

2020

Mol Med Rep

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Matrix metalloproteinase 2 (MMP2) is a well-characterized protein that is indispensable for extracellular matrix remodeling and other pathological processes, such as tumor progression and skeletal dysplasia. Excessive activation of MMP2 promotes osteolytic metastasis and bone destruction in late-stage cancers, while its loss-of-function mutations result in the decreased bone mineralization and generalized osteolysis occurring progressively in skeletal developmental disorders, particularly in multicentric osteolysis, nodulosis and arthropathy (MONA). Either upregulation or downregulation of MMP2 activity can result in the same osteolytic effects. Thus, different functions of MMP2 have been recently identified that could explain this observation. While MMP2 can degrade bone matrix, facilitate osteoclastogenesis and amplify various signaling pathways that enhance osteolysis in bone metastasis, its role in maintaining the number of bone cells, supporting osteocytic canalicular network formation and suppressing leptin-mediated inhibition of bone formation has been implicated in osteolytic disorders caused by MMP2 deficiency. Furthermore, the proangiogenic activity of MMP2 is one of the potential mechanisms that are associated with both pathological situations. In the present article, the latest research on MMP2 in bone homeostasis is reviewed and the mechanisms underlying the role of this protein in skeletal metastasis and developmental osteolysis are discussed.

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Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

Cited by 22 publications

References 93 publications

Matrix Metalloproteinases and Glaucoma Treatment

Matrix Metalloproteinases and Glaucoma Treatment

MMP1 and MMP9 are potential prognostic biomarkers and targets for uveal melanoma

Different roles of matrix metalloproteinase 2 in osteolysis of skeletal dysplasia and bone metastasis (Review)

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