Interaction of the retinoic acid signaling pathway with spicule formation in the marine sponge Suberites domuncula through activation of bone morphogenetic protein-1

The bone morphogenetic protein (BMP) and growth and differentiation factor (GDF) signaling pathways have well-established and essential roles within the developing skeleton in coordinating the formation of cartilaginous anlagen. However, the identification of bona fide targets that underlie the action of these signaling molecules in chondrogenesis has remained elusive. We have identified the gene for the retinoic acid (RA) synthesis enzyme Aldh1a2 as a principal target of BMP signaling; prochondrogenic BMPs or GDFs lead to attenuation of Aldh1a2 expression and, consequently, to reduced activation of the retinoid signaling pathway. Consistent with this, antagonism of retinoid signaling phenocopies BMP4 action, whereas RA inhibits the chondrogenic stimulatory activity of BMP4. BMP4 also down-regulates Aldh1a2 expression in organ culture and, consistent with this, Aldh1a2 is actively excluded from the developing cartilage anlagens. Collectively, these findings provide novel insights into BMP action and demonstrate that BMP signaling governs the fate of prechondrogenic mesenchyme, at least in part, through regulation of retinoid signaling.

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Retinoic acid signaling regulates Sonic hedgehog and bone morphogenetic protein signalings during genital tubercle development

Birth Defects Research Part B Developmental and Reproductive Toxicology ◽

10.1002/bdrb.20344 ◽

2011 ◽

pp. n/a-n/a ◽

Cited By ~ 2

Author(s):

Liqing Liu ◽

Kentaro Suzuki ◽

Naomi Nakagata ◽

Kenichiro Mihara ◽

Daisuke Matsumaru ◽

...

Keyword(s):

Retinoic Acid ◽

Bone Morphogenetic Protein ◽

Sonic Hedgehog ◽

Retinoic Acid Signaling ◽

Morphogenetic Protein ◽

Genital Tubercle

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Bone morphogenetic protein and retinoic acid signaling cooperate to induce osteoblast differentiation of preadipocytes

The Journal of Cell Biology ◽

10.1083/jcb.200204060 ◽

2002 ◽

Vol 159 (1) ◽

pp. 135-146 ◽

Cited By ~ 165

Author(s):

Jeremy Skillington ◽

Lisa Choy ◽

Rik Derynck

Keyword(s):

Retinoic Acid ◽

Bone Morphogenetic Protein ◽

Osteoblast Differentiation ◽

Adipogenic Differentiation ◽

Osteoblastic Differentiation ◽

Mesenchymal Cells ◽

Bmp Signaling ◽

Retinoic Acid Signaling ◽

Morphogenetic Protein ◽

Adipose Conversion

Mesenchymal cells can differentiate into osteoblasts, adipocytes, myoblasts, or chondroblasts. Whether mesenchymal cells that have initiated differentiation along one lineage can transdifferentiate into another is largely unknown. Using 3T3-F442A preadipocytes, we explored whether extracellular signals could redirect their differentiation from adipocyte into osteoblast. 3T3-F442A cells expressed receptors and Smads required for bone morphogenetic protein (BMP) signaling. BMP-2 increased proliferation and induced the early osteoblast differentiation marker alkaline phosphatase, yet only mildly affected adipogenic differentiation. Retinoic acid inhibited adipose conversion and cooperated with BMP-2 to enhance proliferation, inhibit adipogenesis, and promote early osteoblastic differentiation. Expression of BMP-RII together with BMP-RIA or BMP-RIB suppressed adipogenesis of 3T3-F442A cells and promoted full osteoblastic differentiation in response to retinoic acid. Osteoblastic differentiation was characterized by induction of cbfa1, osteocalcin, and collagen I expression, and extracellular matrix calcification. These results indicate that 3T3-F442A preadipocytes can be converted into fully differentiated osteoblasts in response to extracellular signaling cues. Furthermore, BMP and retinoic acid signaling cooperate to stimulate cell proliferation, repress adipogenesis, and promote osteoblast differentiation. Finally, BMP-RIA and BMP-RIB induced osteoblast differentiation and repressed adipocytic differentiation to a similar extent.

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