Evidence map›Paper›PMID 18765931›Full record

ArticleCells, tissues, organs2009

1,25-Dihydroxy vitamin D3 is an autocrine regulator of extracellular matrix turnover and growth factor release via ERp60-activated matrix vesicle matrix metalloproteinases.

B D Boyan, Z Schwartz

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, tissues, organs, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 26 citations in OpenAlex.

  1. Trial
  2. ER-resident proteins are key players in cartilage and bone homeostasis.Frontiers in cell and developmental biology · 2025
    Review
  3. 1α,25-Dihydroxyvitamin DCalcified tissue international · 2023
    Article
  4. Article
  5. Effects of 1,25-Dihydroxy vitamin DMolecular and cellular biochemistry · 2020
    Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Role of matrix vesicles in biomineralization.Biochimica et biophysica acta · 2009
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 1 country.

B D BoyanWallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, Ga. 30332-0363, USA. barbara.boyan@bme.gatech.edu
Z Schwartz
Georgia Institute of Technology · USThe Wallace H. Coulter Department of Biomedical Engineering · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

As growth plate chondrocytes mature and hypertrophy, they reorganize their proteoglycan-rich type II collagen extracellular matrix (ECM), involving 1,25(OH)(2)D(3)-dependent regulation of matrix metalloproteinases (MMPs). Stromelysin-1 (MMP-3) and 72-kD gelatinase (MMP-2) are found in extracellular matrix vesicles (MVs) and release and activate ECM-bound latent TGF-beta1 and TGF-beta2, respectively. 1,25(OH)(2)D(3) regulates incorporation of MMP-2 and MMP-3 into MVs and release of these enzymes in the ECM. Plasma membranes (PMs) and MVs contain the 1alpha,25(OH)(2)D(3) membrane receptor ERp60 (protein disulfide isomerase A3), phospholipase A(2) (PLA(2)), PLA(2)-activating protein, the nuclear vitamin D receptor and caveolin-1. 1,25(OH)(2)D(3) secreted by chondrocytes binds MV ERp60, activating PLA(2). Resulting lysophospholipids destabilize MV membranes, releasing active MMPs. We examined 1,25(OH)(2)D(3)-dependent activation of latent TGF-beta1 stored in cartilage ECM. Interestingly, TGF-beta1 regulates 1,25(OH)(2)D(3) production. 1alpha,25(OH)(2)D(3) activates PM protein kinase C (PKC)-alpha via ERp60-dependent PLA(2)-signaling, lysophospholipid production and phospholipase C-gamma. It also regulates distribution of phospholipids and PKC isoforms between MVs and PMs, enriching MVs in PKC-zeta. Direct activation of MV MMP-3 requires ERp60 based on blocking antibodies and PKC based on inhibitor studies. However, treatment of MVs with 1,25(OH)(2)D(3) decreases MV PKC-zeta activity, suggesting more complex feedback mechanisms, potentially involving MV lipid signaling. Our observations indicate that one role of MVs is to provide MMPs at sites distant from the cells. Chondrocytes secrete 1,25(OH)(2)D(3), which acts directly on MV-membranes via ERp60, releasing MMPs. MMP-specific ECM components are hydrolyzed, resulting in release and activation of growth factors that can act back on the cells.

Indexed as

AnimalsAutocrine CommunicationCalreticulinCaveolin 1Cell ExtractsChondrocytesEnzyme ActivationExtracellular MatrixGrowth PlateIntercellular Signaling Peptides and ProteinsMatrix Metalloproteinase 2Matrix Metalloproteinase 3Matrix MetalloproteinasesRatsReceptors, CalcitriolSecretory VesiclesCalreticulinCaveolin 1Cell Extractsdihydroxy-vitamin D3Intercellular Signaling Peptides and ProteinsMatrix Metalloproteinase 2Matrix Metalloproteinase 3Matrix MetalloproteinasesReceptors, CalcitriolTransforming Growth Factor betaVitamin D

Identifiers

PMID18765931
PMCPMC2824185
OpenAlexW1976183788

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.