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Bone morphogenetic proteins (BMPs) have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors (BMPRI and BMPRII). In recent decades, genetic studies in humans and mice have demonstrated that perturbations in BMP signaling via BMPRI resulted in various diseases in bone, cartilage, and muscles. In this review, we focus on all three types of BMPRI, which consist of activin-like kinase 2 (ALK2, also called type IA activin receptor), activin-like kinase 3 (ALK3, also called BMPRIA), and activin-like kinase 6 (ALK6, also called BMPRIB). The research areas covered include the current progress regarding the roles of these receptors during myogenesis, chondrogenesis, and osteogenesis. Understanding the physiological and pathological functions of these receptors at the cellular and molecular levels will advance drug development and tissue regeneration for treating musculoskeletal diseases and bone defects in the future.
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http://dx.doi.org/10.1038/boneres.2016.5 | DOI Listing |
Cells
September 2024
Department of Ophthalmology, University of Cincinnati, Cincinnati, OH 45267, USA.
The synthetic peptide of lumican C-terminal 13 amino acids with the cysteine replaced by an alanine, hereafter referred to as lumikine (LumC13: YEALRVANEVTLN), binds to TGFβ type I receptor/activin-like kinase5 (TBR1/ALK5) in the activated TGFβ receptor complex to promote corneal epithelial wound healing. The present study aimed to identify the minimum essential amino acid epitope necessary to exert the effects of lumikine via ALK5 and to determine the role of the Y (tyrosine) residue for promoting corneal epithelium wound healing. This study also aimed to determine the signaling pathway(s) triggered by lumican-ALK5 binding.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
October 2024
Pfizer Worldwide Research and Development, La Jolla, California (M.G., S.T., T.R.J., A.V., T.F., M.F.); 1cBio, Inc., Moraga, California (S.P.); Fundación Ciencia & Vida, Santiago, Chile (S.B.); Merck Research Laboratories, South San Francisco, California (R.P.); and Trancura Biosciences, Alameda, California (F.J.H.).
The development of transforming growth factor receptor inhibitors (TGFRi) as new medicines has been affected by cardiac valvulopathy and arteriopathy toxicity findings in nonclinical toxicology studies. PF-06952229 (MDV6058) selected using rational drug design is a potent and selective TGFRI inhibitor with a relatively clean off-target selectivity profile and good pharmacokinetic properties across species. PF-06952229 inhibited clinically translatable phospho-SMAD2 biomarker (≥60%) in human and cynomolgus monkey peripheral blood mononuclear cells, as well as in mouse and rat splenocytes.
View Article and Find Full Text PDFTheriogenology
September 2024
Department of Bioproduction, Graduate School of Bioindustry, Tokyo University of Agriculture, Abashiri, Hokkaido, 099-2493, Japan; Department of Bioproduction, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri, Hokkaido, 099-2493, Japan. Electronic address:
Although anti-Müllerian hormone (AMH) is involved in the regulation of granulosa cell function in female animals, its role in tissues other than ovarian follicles remains poorly understood. It has also been suggested that cows with high circulating AMH concentrations have increased fertility; however, the mechanism has not been elucidated. This study was conducted to identify the presence of the AMH-signaling system and its target cells in the bovine corpus luteum formed from an ovulated follicle.
View Article and Find Full Text PDFPLoS One
June 2024
Department of Biochemistry, Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee, United States of America.
Biomolecules
March 2024
Center for Organogenesis, Regeneration, and Trauma, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Heterotopic ossification (HO) is a debilitating pathology where ectopic bone develops in areas of soft tissue. HO can develop as a consequence of traumatic insult or as a result of dysregulated osteogenic signaling, as in the case of the orphan disease fibrodysplasia ossificans progressiva (FOP). Traumatic HO (tHO) formation is mediated by the complex interplay of signaling between progenitor, inflammatory, and nerve cells, among others, making it a challenging process to understand.
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