The Biological Function of Type I Receptors of Bone Morphogenetic Protein in Bone

Overview

Journal Bone Res

Specialties Endocrinology
Orthopedics

Date 2016 Apr 19

PMID 27088043

Citations 29

Authors

Shuxian Lin

Kathy K H Svoboda

Jian Q Feng

Xinquan Jiang

Affiliations

Soon will be listed here.

Abstract

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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References

Yamashita M, Otsuka F, Mukai T, Yamanaka R, Otani H, Matsumoto Y . Simvastatin inhibits osteoclast differentiation induced by bone morphogenetic protein-2 and RANKL through regulating MAPK, AKT and Src signaling. Regul Pept. 2010; 162(1-3):99-108. DOI: 10.1016/j.regpep.2010.03.003. View

Culbert A, Chakkalakal S, Theosmy E, Brennan T, Kaplan F, Shore E . Alk2 regulates early chondrogenic fate in fibrodysplasia ossificans progressiva heterotopic endochondral ossification. Stem Cells. 2014; 32(5):1289-300. PMC: 4419363. DOI: 10.1002/stem.1633. View

Gregson C, Hollingworth P, Williams M, Petrie K, Bullock A, Brown M . A novel ACVR1 mutation in the glycine/serine-rich domain found in the most benign case of a fibrodysplasia ossificans progressiva variant reported to date. Bone. 2010; 48(3):654-8. PMC: 3160462. DOI: 10.1016/j.bone.2010.10.164. View

Baur S, Mai J, Dymecki S . Combinatorial signaling through BMP receptor IB and GDF5: shaping of the distal mouse limb and the genetics of distal limb diversity. Development. 2000; 127(3):605-19. DOI: 10.1242/dev.127.3.605. View

Nakamura A, Ly C, Cipetic M, Sims N, Vieusseux J, Kartsogiannis V . Osteoclast inhibitory lectin (OCIL) inhibits osteoblast differentiation and function in vitro. Bone. 2006; 40(2):305-15. DOI: 10.1016/j.bone.2006.09.001. View

Agarwal S, Loder S, Brownley C, Eboda O, Peterson J, Hayano S . BMP signaling mediated by constitutively active Activin type 1 receptor (ACVR1) results in ectopic bone formation localized to distal extremity joints. Dev Biol. 2015; 400(2):202-9. PMC: 4397658. DOI: 10.1016/j.ydbio.2015.02.011. View

Park D, Spencer J, Koh B, Kobayashi T, Fujisaki J, Clemens T . Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration. Cell Stem Cell. 2012; 10(3):259-72. PMC: 3652251. DOI: 10.1016/j.stem.2012.02.003. View

Gautschi O, Frey S, Zellweger R . Bone morphogenetic proteins in clinical applications. ANZ J Surg. 2007; 77(8):626-31. DOI: 10.1111/j.1445-2197.2007.04175.x. View

Ten Dijke P, Yamashita H, Sampath T, Reddi A, Estevez M, Riddle D . Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4. J Biol Chem. 1994; 269(25):16985-8. View

10.

Kaplan J, Kaplan F, Shore E . Restoration of normal BMP signaling levels and osteogenic differentiation in FOP mesenchymal progenitor cells by mutant allele-specific targeting. Gene Ther. 2011; 19(7):786-90. PMC: 3390458. DOI: 10.1038/gt.2011.152. View

11.

Zhang D, Schwarz E, Rosier R, Zuscik M, Puzas J, OKeefe R . ALK2 functions as a BMP type I receptor and induces Indian hedgehog in chondrocytes during skeletal development. J Bone Miner Res. 2003; 18(9):1593-604. DOI: 10.1359/jbmr.2003.18.9.1593. View

12.

Moester M, Papapoulos S, Lowik C, Van Bezooijen R . Sclerostin: current knowledge and future perspectives. Calcif Tissue Int. 2010; 87(2):99-107. PMC: 2903685. DOI: 10.1007/s00223-010-9372-1. View

13.

Furuya H, Ikezoe K, Wang L, Ohyagi Y, Motomura K, Fujii N . A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H). Am J Med Genet A. 2008; 146A(4):459-63. DOI: 10.1002/ajmg.a.32151. View

14.

Yoon B, Ovchinnikov D, Yoshii I, Mishina Y, Behringer R, Lyons K . Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo. Proc Natl Acad Sci U S A. 2005; 102(14):5062-7. PMC: 555995. DOI: 10.1073/pnas.0500031102. View

15.

Glass 2nd D, Bialek P, Ahn J, Starbuck M, Patel M, Clevers H . Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell. 2005; 8(5):751-64. DOI: 10.1016/j.devcel.2005.02.017. View

16.

Yi S, Daluiski A, Pederson R, Rosen V, Lyons K . The type I BMP receptor BMPRIB is required for chondrogenesis in the mouse limb. Development. 2000; 127(3):621-30. DOI: 10.1242/dev.127.3.621. View

17.

Urist M . Bone: formation by autoinduction. Science. 1965; 150(3698):893-9. DOI: 10.1126/science.150.3698.893. View

18.

Petrie K, Lee W, Bullock A, Pointon J, Smith R, Russell R . Novel mutations in ACVR1 result in atypical features in two fibrodysplasia ossificans progressiva patients. PLoS One. 2009; 4(3):e5005. PMC: 2658887. DOI: 10.1371/journal.pone.0005005. View

19.

Kamiya N, Ye L, Kobayashi T, Mochida Y, Yamauchi M, Kronenberg H . BMP signaling negatively regulates bone mass through sclerostin by inhibiting the canonical Wnt pathway. Development. 2008; 135(22):3801-11. PMC: 2694443. DOI: 10.1242/dev.025825. View

20.

Chen D, Ji X, Harris M, Feng J, Karsenty G, Celeste A . Differential roles for bone morphogenetic protein (BMP) receptor type IB and IA in differentiation and specification of mesenchymal precursor cells to osteoblast and adipocyte lineages. J Cell Biol. 1998; 142(1):295-305. PMC: 2133031. DOI: 10.1083/jcb.142.1.295. View