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Ectopic expression of recombinant human bone morphogenetic protein 2 (rhBMP2) induces osteogenesis, while ectopic expression of rhBMP12 and rhBMP13 induces the formation of tendon-like tissue. Despite their different in vivo activities, all three ligands bound to the type I bone morphogenic protein receptors (BMPRs), activin receptor-like kinase (ALK)-3 and ALK6, and to the type II BMPRs, activin receptor type-2A, activin receptor type-2B, and BMPR2, with similar affinities. Treatment of C3H10T1/2 cells with rhBMP2 activated SMAD signaling and induced expression of osteoblast markers including osteocalcin mRNA (Ocn). In contrast, treatment with rhBMP12 or rhBMP13 resulted in a dose-dependent induction of a tendon-specific gene (Thbs4) expression with no detectable activation of SMAD 1, 5, and 8. Differential regulation of Thbs4 and Ocn has potential utility as an in vitro biomarker for induction of tenogenic signaling. Such an assay also permits the ability to distinguish between the activities of different BMPs and may prove useful in studies on the molecular mechanisms of BMP tenogenic activity.

Activin is a member of the TGF-beta superfamily and has various effects on diverse biological systems. Activins initiate their cellular responses by binding to their receptors with intrinsic serine/threonine kinase activity and activation of specific downstream intracellular effectors termed Smad proteins. Smads relay the signal from the cell membrane to the nucleus, where they affect the transcription of target genes. Negative regulation of activin signal occurs at the extracellular, membrane, cytoplasmic and nuclear levels. The presence of many mechanisms for regulation shows its importance to normal physiology. Here, we review the latest advances in activin signal transduction.

Inhibin is best known as a reproductive hormone that inhibits release of follicle-stimulating hormone (FSH) from the pituitary gland. Over the last decade or so a number of other biological roles have emerged, putting inhibin more in the class of a growth factor. Despite this, little is known of the signalling pathways for this protein. This minireview summarises the pertinent aspects of inhibin biology and focuses on four potential signalling mechanisms through which inhibin might influence cellular function, namely subunit availability, receptor assembly, co-receptors and signalling through inhibin-specific signalling pathways.