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GP130/OSMR is the only LIF/IL‐6 family receptor complex to promote osteoblast differentiation of calvaria progenitors
Author(s) -
Malaval Luc,
Liu Fina,
Vernallis Ann B.,
Aubin Jane E.
Publication year - 2005
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20312
Subject(s) - leukemia inhibitory factor receptor , leukemia inhibitory factor , oncostatin m , bone sialoprotein , glycoprotein 130 , osteoblast , cellular differentiation , endocrinology , medicine , biology , microbiology and biotechnology , calvaria , signal transduction , chemistry , osteocalcin , cytokine , immunology , stat3 , in vitro , biochemistry , interleukin 6 , alkaline phosphatase , gene , enzyme
Leukemia inhibitory factor (LIF) and its receptor (LIFR) are “twins” of Oncostatin M (OSM) and OSMR, respectively, likely having arisen through gene duplications. We compared their effects in a bone nodule‐forming model of in vitro osteogenesis, rat calvaria (RC) cell cultures. Using a dominant‐negative LIF mutant (hLIF‐05), we showed that in RC cell cultures mouse OSM (mOSM) activates exclusively glycoprotein 130 (gp130)/OSMR. In treatments starting at early nodule formation stage, LIF, mOSM, IL‐11, and IL‐6 + sIL‐6R inhibit bone nodule formation, that is, osteoprogenitor differentiation. Treatment with mOSM, and no other cytokine of the family, in early cultures (day 1–3 or 1–4) increases bone colony numbers. hLIF‐05 also dose dependently stimulates bone nodule formation, confirming the inhibitory action of gp130/LIFR on osteogenesis. In pulse treatments at successive stages of bone nodule formation and maturation, LIF blocks osteocalcin (OCN) expression by differentiated osteoblasts, but has no effect on bone sialoprotein (BSP) expression. Mouse OSM inhibits OCN and BSP expression in preconfluent cultures with no or progressively reduced effects at later stages, reflecting the disruption of early nodules, possibly due to the strong apoptotic action of mOSM in RC cell cultures. In summary, LIFR and OSMR display differential effects on differentiation and phenotypic expression of osteogenic cells, most likely through different signal transduction pathways. In particular, gp130/OSMR is the only receptor complex of the family to stimulate osteoprogenitor differentiation in the RC cell culture model. © 2005 Wiley‐Liss, Inc.