期刊
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 103, 期 3-5, 页码 467-472出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2006.11.003
关键词
1 alpha,25(OH)(2)D-3; matrix vesicles; growth plate chondrocytes; rapid actions matrix metalloproteinases; TGF-beta 1 activation; TGF-beta 2
资金
- NIDCR NIH HHS [R01 DE008603-12, R01 DE008603, R01 DE005937-19] Funding Source: Medline
Growth plate chondrocytes produce proteoglycan-rich type II collagen extracellular matrix (ECM). During cell maturation and hypertrophy, ECM is reorganized via a process regulated by 1 alpha,25(OH)(2)D-3 and involving matrix metalloprotemases (MMPs), including MMP-3 and MMP2. 1 alpha,25(OH)(2)D-3 regulates MMP incorporation into matrix vesicles (MVs), where they are stored until released. Like plasma membranes (PM). MVs contain the 1 alpha.25(OH)(2)D-3-binding protein ERp60, phospholipase A(2) (PLA(2)), and caveolin-1, but appear to lack nuclear Vitamin D receptors (VDRs). Chondrocytes produce 1 alpha,25(OH)(2)D-3 (10(-8) M), which binds ERp60, activating PLA(2), and resulting lysophospholipids lead to MV membrane disorganization, releasing active MMPs. MV MMP-3 activates TGF-beta 1 stored in the ECM as large latent TGF-beta 1 complexes. consisting of latent TGF-beta 1 binding protein, latency associated peptide, and latent TGF-beta 1. Others have shown that MMP2 specifically activates TGF-beta 2. TGF-beta 1 regulates 1 alpha,25(OH)(2)D-3-production, providing a mechanism for local control of growth factor activation. 1 alpha,25(OH)(2)D-3 activates PKCu in the PM via ERp60-signaling through PLA2, lysophospholipid production, and PLC beta. It also regulates distribution of phospholipids and PKC isoforms between MVs and PMs, enriching the MVs in PKCC. Direct activation of MMP-3 in MVs requires ERp60. However, when MVs are treated with 1 alpha,25(OH)(2)D-3, PKCC activity is decreased and PKCa is unaffected, suggesting a more complex feedback mechanism, potentially involving MV lipid signaling. (c) 2006 Elsevier Ltd. All rights reserved.
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