Steroid hormone action in musculoskeletal cells involves membrane receptor and nuclear receptor mechanisms

Barbara D. Boyan, David D. Dean, Victor L. Sylvia, Zvi Schwartz

Research output: Contribution to journalReview articlepeer-review

17 Scopus citations

Abstract

Steroid hormones regulate target cells through traditional nuclear mechanisms as well as by membrane mechanisms. 1α,25(OH)2D3 and 24R,25(OH)2D3 bind membrane receptors (mVDR) and mediate their effects on the physiological responses of musculoskeletal cells via protein kinase C (PKC). In cultures of costochondral growth plate chondrocytes, 1α,25(OH)2D3 binds the 1,25-mVDR in growth zone cells, activating phospholipase C (PLC), leading to diacylglycerol (DAG) production and PKC translocation to the plasma membrane. It also activates PLA2, increasing arachidonic acid release and prostaglandin synthesis. 24R,25(OH)2D3 binds its membrane receptor in resting zone chondrocytes, activating phospholipase D (PLD), and increasing DAG and PKC activity, but translocation does not occur. PLA2 activity is decreased, reducing arachidonic acid and prostaglandin production. 17Β-Estradiol (E2) activates PKC in both cartilage cells, but DAG is not involved. 1α,25(OH)2D3 and 24R,25(OH)2D3 also increase PKC in osteoblasts in a cell-specific manner. Antibodies to the 1,25-mVDR block PKC activation. Membrane-mediated events influence gene expression via signaling cascades, including the ERK1/2 MAP kinases. The ability of steroid hormones to initiate events nongenomically is important for regulation of matrix vesicle (MV) function in the extracellular matrix. MVs have mVDRs, but ligand binding inhibits PKC-zeta (PKCζ) via a mechanism that differs from PKCα activation in the plasma membranes. Treatment of MVs from growth zone chondrocyte cultures with 1α,25(OH)2D3 releases stromelysin-1 (MMP-3) and increases TGF-β activation. MMP-3 is also involved in proteoglycan degradation, facilitating calcification. 24R,-25(OH)2D3 inhibits PKCζ in MV from resting zone cell cultures and inhibits MMP-3 release. Chondrocytes and osteoblasts produce 1,25(OH)2D3, 24,25(OH)2D3, and E2; thus, locally produced steroids may function as autocrine regulators of matrix events, including matrix vesicle enzyme activity and matrix protein remodelling during longitudinal growth, calcification, and growth factor activation.

Original languageEnglish (US)
Pages (from-to)130-135
Number of pages6
JournalConnective Tissue Research
Volume44
Issue numberSUPPL. 1
DOIs
StatePublished - 2003

Keywords

  • 1α,25(OH)D
  • 24R,25(OH)D
  • Estrogen
  • MAP kinase
  • Protein kinase C
  • Rapid actions

ASJC Scopus subject areas

  • Rheumatology
  • Biochemistry
  • Orthopedics and Sports Medicine
  • Molecular Biology
  • Cell Biology

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