Abstract
Septoclasts, which are mononuclear and spindle-shaped cells with many processes, have been considered to resorb the transverse septa of the growth plate (GP) cartilage at the chondro-osseous junction (COJ). We previously reported the expression of epidermal-type fatty acid-binding protein (E-FABP, FABP5) and localization of peroxisome proliferator-activated receptor (PPAR)β/δ, which mediates the cell survival or proliferation, in septoclasts. On the other hand, retinoic acid (RA) can bind to E-FABP and is stored abundantly in the GP cartilage. From these information, it is possible to hypothesize that RA in the GP is incorporated into septoclasts during the cartilage resorption and regulates the growth and/or death of septoclasts. To clarify the mechanism of the cartilage resorption induced by RA, we administered an overdose of RA or its precursor vitamin A (VA)-deficient diet to young mice. In mice of both RA excess and VA deficiency, septoclasts decreased in the number and cell size in association with shorter and lesser processes than those in normal mice, suggesting a substantial suppression of resorption by septoclasts in the GP cartilage. Lack of PPARβ/δ-expression, TUNEL reaction, RA receptor (RAR)β, and cellular retinoic acid-binding protein (CRABP)-II were induced in E-FABP-positive septoclasts under RA excess, suggesting the growth arrest/cell-death of septoclasts, whereas cartilage-derived retinoic acid-sensitive protein (CD-RAP) inducing the cell growth arrest or morphological changes was induced in septoclasts under VA deficiency. These results support and do not conflict with our hypothesis, suggesting that endogenous RA in the GP is possibly incorporated in septoclasts and utilized to regulate the activity of septoclasts resorbing the GP cartilage.
Highlights
Septoclasts, previously termed perivascular cells, are located at the chondro-osseous junction (COJ) between the growth plate (GP) cartilage and the metaphysis (Schenk et al 1967; Lee et al 1995; Nakamura and Ozawa 1996)
Major findings of the present study are the decrease in number of E-Fatty acid-binding proteins (FABPs)-positive septoclasts being simultaneously immunopositive for PPARβ/δ, and the increase in number of E-FABP-positive septoclasts showing TUNEL-positive apoptosis or immunoreactivities for RARβ and cellular retinoic acid-binding protein (CRABP)-II by means of administration of mice under retinoic acid (RA) excess
RA as well as FAs is known to be an agonist of PPARβ/δ, and to induce the cell survival/proliferation via a signaling pathway mediated by E-FABP and PPARβ/δ (Schug et al 2007)
Summary
Septoclasts, previously termed perivascular cells, are located at the chondro-osseous junction (COJ) between the growth plate (GP) cartilage and the metaphysis (Schenk et al 1967; Lee et al 1995; Nakamura and Ozawa 1996). Enzymes working in degradation of the uncalcified cartilage matrix such as cathepsin B (Lee et al 1995) and matrix metalloproteinase (MMP)-13 (Nakamura et al 2004) have been detected in septoclasts. Histological and biochemical features above have suggested that septoclasts resorb the uncalcified cartilage matrices at the GP (Lee et al 1995). We previously reported exclusive expression and localization of epidermal-type fatty acid-binding protein (E-FABP, FABP5) in septoclasts in the GP of mice (Bando et al 2014).
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