Filamin B: The next hotspot in skeletal research?

Qiming Xu^{a, #},
Nan Wu^{a, b, c, #},
Lijia Cui^{d, e},
Zhihong Wu^{b, c, f},
Guixing Qiu^{a, b, c
, ,}

a.
Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
b.
Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China
c.
Medical Research Center of Orthopaedics, Chinese Academy of Medical Sciences, Beijing 100730, China
d.
Peking Union Medical College Hospital, Beijing 100730, China
e.
School of Medicine, Tsinghua University, Beijing 100084, China
f.
Department of Central Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China

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Corresponding author: E-mail address: qiuguixingpumch@126.com (Guixing Qiu)

These authors contributed equally to this work.

摘要

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Abstract: Filamin B (FLNB) is a large dimeric actin-binding protein which crosslinks actin cytoskeleton filaments into a dynamic structure. Up to present, pathogenic mutations in FLNB are solely found to cause skeletal deformities, indicating the important role of FLNB in skeletal development. FLNB-related disorders are classified as spondylocarpotarsal synostosis (SCT), Larsen syndrome (LS), atelosteogenesis (AO), boomerang dysplasia (BD), and isolated congenital talipes equinovarus, presenting with scoliosis, short-limbed dwarfism, clubfoot, joint dislocation and other unique skeletal abnormalities. Several mechanisms of FLNB mutations causing skeletal malformations have been proposed, including delay of ossification in long bone growth plate, reduction of bone mineral density (BMD), dysregulation of muscle differentiation, ossification of intervertebral disc (IVD), disturbance of proliferation, differentiation and apoptosis in chondrocytes, impairment of angiogenesis, and hypomotility of osteoblast, chondrocyte and fibroblast. Interventions on FLNB-related diseases require prenatal surveillance by sonography, gene testing in high-risk carriers, and proper orthosis or orthopedic surgeries to correct malformations including scoliosis, cervical spine instability, large joint dislocation, and clubfoot. Gene and cell therapies for FLNB-related diseases are also promising but require further studies.
- Filamin B /
- Spondylocarpotarsal synostosis /
- Larsen syndrome /
- Scoliosis /
- Skeletal development
These authors contributed equally to this work.
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参考文献(66)

[1]	Akbarnia, B.A., Moe, J.H. Familial congenital scoliosis with unilateral unsegemented bar. Case report of two siblings J. Bone Jt. Surg. Am., 60 (1978),pp. 259-261
[2]	Becker, R., Wegner, R.D., Kunze, J. et al. Clinical variability of Larsen syndrome: diagnosis in a father after sonographic detection of a severely affected fetus Clin. Genet., 57 (2000),pp. 148-150
[3]	Bello, N.F., Lamsoul, I., Heuze, M.L. et al. The E3 ubiquitin ligase specificity subunit ASB2beta is a novel regulator of muscle differentiation that targets filamin B to proteasomal degradation Cell Death Differ., 16 (2009),pp. 921-932
[4]	Bicknell, L.S., Farrington-Rock, C., Shafeghati, Y. et al. J. Med. Genet., 44 (2007),pp. 89-98
[5]	Brocker, F., Bardenheuer, W., Vieten, L. et al. Cytogenet. Cell Genet., 85 (1999),pp. 267-268
[6]	Daniel, P.B., Morgan, T., Alanay, Y. et al. Disease-associated mutations in the actin-binding domain of filamin B cause cytoplasmic focal accumulations correlating with disease severity Hum. Mutat., 33 (2012),pp. 665-673
[7]	Debeer, P., De Borre, L., De Smet, L. et al. Asymmetrical Larsen syndrome in a young girl: a second example of somatic mosaicism in this syndrome Genet. Couns., 14 (2003),pp. 95-100
[8]	Del Valle-Perez, B., Martinez, V.G., Lacasa-Salavert, C. et al. Filamin B plays a key role in vascular endothelial growth factor-induced endothelial cell motility through its interaction with Rac-1 and Vav-2 J. Biol. Chem., 285 (2010),pp. 10748-10760
[9]	Dobbs, M.B., Boehm, S., Grange, D.K. et al. Case report: congenital knee dislocation in a patient with Larsen syndrome and a novel filamin B mutation Clin. Orthop. Relat. Res., 466 (2008),pp. 1503-1509
[10]	Farrington-Rock, C., Firestein, M.H., Bicknell, L.S. et al. Hum. Mutat., 27 (2006),pp. 705-710
[11]	Farrington-Rock, C., Kirilova, V., Dillard-Telm, L. et al. Hum. Mol. Genet., 17 (2008),pp. 631-641
[12]	Forlino, A., Marini, J.C. Osteogenesis imperfecta Lancet, 387 (2016),pp. 1657-1671
[13]	Frints, S.G., De Smet, L., Fabry, G. et al. A young female with asymmetric manifestations of Larsen syndrome: another example of unilateral somatic cell-line mosaicism Clin. Dysmorphol., 9 (2000),pp. 273-276
[14]	Gardel, M.L., Schneider, I.C., Aratyn-Schaus, Y. et al. Mechanical integration of actin and adhesion dynamics in cell migration Annu. Rev. Cell Dev. Biol., 26 (2010),pp. 315-333
[15]	Girisha, K.M., Bidchol, A.M., Graul-Neumann, L. et al. Phenotype and genotype in patients with Larsen syndrome: clinical homogeneity and allelic heterogeneity in seven patients BMC Med. Genet., 17 (2016),p. 27
[16]	Gorlin, J.B., Yamin, R., Egan, S. et al. Human endothelial actin-binding protein (ABP-280, nonmuscle filamin): a molecular leaf spring J. Cell Biol., 111 (1990),pp. 1089-1105
[17]	Guo, Y., Zhang, S.X., Sokol, N. et al. J. Cell Sci., 113 (2000),pp. 3499-3508
[18]	Hartwig, J.H., Stossel, T.P. Isolation and properties of actin, myosin, and a new actinbinding protein in rabbit alveolar macrophages J. Biol. Chem., 250 (1975),pp. 5696-5705
[19]	Hou, Z., Nguyen, Q., Frenkel, B. et al. Osteoblast-specific gene expression after transplantation of marrow cells: implications for skeletal gene therapy Proc. Natl. Acad. Sci. U. S. A., 96 (1999),pp. 7294-7299
[20]	Hu, J., Lu, J., Lian, G. et al. Formin 1 and filamin B physically interact to coordinate chondrocyte proliferation and differentiation in the growth plate Hum. Mol. Genet., 23 (2014),pp. 4663-4673
[21]	Hu, J., Lu, J., Lian, G. et al. Filamin B regulates chondrocyte proliferation and differentiation through Cdk1 signaling PLoS One, 9 (2014),p. e89352
[22]	Isidor, B., Cormier-Daire, V., Le Merrer, M. et al. Autosomal dominant spondylocarpotarsal synostosis syndrome: phenotypic homogeneity and genetic heterogeneity Am. J. Med. Genet. A, 146a (2008),pp. 1593-1597
[23]	Jeon, G.W., Lee, M.N., Jung, J.M. et al. Ann. Lab. Med., 34 (2014),pp. 134-138
[24]	, Birch, J.G., Daniels, J.L. Cervical kyphosis in patients who have Larsen syndrome J. Bone Jt. Surg. Am., 78 (1996),pp. 538-545
[25]	Kozlowski, K., Sillence, D., Cortis-Jones, R. et al. Boomerang dysplasia Br. J. Radiol., 58 (1985),pp. 369-371
[26]	Kozlowski, K., Tsuruta, T., Kameda, Y. et al. New forms of neonatal death dwarfism. Report of 3 cases Pediatr. Radiol., 10 (1981),pp. 155-160
[27]	Krakow, D., Robertson, S.P., King, L.M. et al. Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis Nat. Genet., 36 (2004),pp. 405-410
[28]	, Gorlin, R.J., Donnai, D., Hamel, B.C. et al. Spondylocarpotarsal synostosis syndrome (with or without unilateral unsegmented bar) Am. J. Med. Genet., 51 (1994),pp. 1-8
[29]	Larsen, L.J., Schottstaedt, E.R., Bost, F.C. Multiple congenital dislocations associated with characteristic facial abnormality J. Pediatr., 37 (1950),pp. 574-581
[30]	Li, G.H., Kung, A.W., Huang, Q.Y. Osteoporos. Int., 21 (2010),pp. 1009-1020
[31]	Liu, Y., Zhao, D., Zhao, L. et al. Congenital Clubfoot: early recognition and conservative management for preventing late disabilities Indian J. Pediatr., 83 (2016),pp. 1266-1274
[32]	Lu, J., Lian, G., Lenkinski, R. et al. Filamin B mutations cause chondrocyte defects in skeletal development Hum. Mol. Genet., 16 (2007),pp. 1661-1675
[33]	Lynch, C.D., Gauthier, N.C., Biais, N. et al. Filamin depletion blocks endoplasmic spreading and destabilizes force-bearing adhesions Mol. Biol. Cell, 22 (2011),pp. 1263-1273
[34]	Makitie, O., Savarirayan, R., Bonafe, L. et al. Am. J. Med. Genet. A, 122A (2003),pp. 187-192
[35]	Marom, R., Lee, Y.C., Grafe, I. et al. Pharmacological and biological therapeutic strategies for osteogenesis imperfecta Am. J. Med. Genet. C Semin. Med. Genet., 172 (2016),pp. 367-383
[36]	Maroteaux, P., Spranger, J., Stanescu, V. et al. Atelosteogenesis Am. J. Med. Genet., 13 (1982),pp. 15-25
[37]	Mizuhashi, K., Kanamoto, T., Moriishi, T. et al. Filamin-interacting proteins, Cfm1 and Cfm2, are essential for the formation of cartilaginous skeletal elements Hum. Mol. Genet., 23 (2014),pp. 2953-2967
[38]	Nakamura, F., Stossel, T.P., Hartwig, J.H. The filamins: organizers of cell structure and function Cell adh. Migr., 5 (2011),pp. 160-169
[39]	Niyibizi, C., Wang, S., Mi, Z. et al. Gene therapy approaches for osteogenesis imperfecta Gene Ther., 11 (2004),pp. 408-416
[40]	Odent, S., Loget, P., Le Marec, B. et al. Unusual fan shaped ossification in a female fetus with radiological features of boomerang dysplasia J. Med. Genet., 36 (1999),pp. 330-332
[41]	Petrella, R., Rabinowitz, J.G., Steinmann, B. et al. Long-term follow-up of two sibs with Larsen syndrome possibly due to parental germ-line mosaicism Am. J. Med. Genet., 47 (1993),pp. 187-197
[42]	Popowicz, G.M., Schleicher, M., Noegel, A.A. et al. Filamins: promiscuous organizers of the cytoskeleton Trends biochem. Sci., 31 (2006),pp. 411-419
[43]	Robertson, S.
[44]	Sarikaya, I.A., Gorgun, B., Erdal, O.A. Atelosteogenesis type III: orthopedic management J. Pediatr. Orthop. B (2016)
[45]	Sawyer, G.M., Clark, A.R., Robertson, S.P. et al. Disease-associated substitutions in the filamin B actin binding domain confer enhanced actin binding affinity in the absence of major structural disturbance: insights from the crystal structures of filamin B actin binding domains J. Mol. Biol., 390 (2009),pp. 1030-1047
[46]	Sibley, C.R., Wood, M.J. The miRNA pathway in neurological and skeletal muscle disease: implications for pathogenesis and therapy J. Mol. Med. (Berl.), 89 (2011),pp. 1065-1077
[47]	Smith, W.G. Interventions for congenital talipes equinovarus (clubfoot) Paediatr. Child. Health, 20 (2015),pp. 307-308
[48]	Sneha, P., Thirumal, K.D., Himani, T. et al. J. Cell. Biochem., 118 (2017),pp. 1900-1910
[49]	Stanley, C.S., Thelin, J.W., Miles, J.H. Mixed hearing loss in Larsen syndrome Clin. Genet., 33 (1988),pp. 395-398
[50]	Stern, H.J., , Lachman, R.S., Horton, W. et al. Atelosteogenesis type III: a distinct skeletal dysplasia with features overlapping atelosteogenesis and oto-palato-digital syndrome type II Am. J. Med. Genet., 36 (1990),pp. 183-195
[51]	Stossel, T.P., Condeelis, J., Cooley, L. et al. Filamins as integrators of cell mechanics and signalling Nat. Rev. Mol. Cell Biol., 2 (2001),pp. 138-145
[52]	Su, Y.T., Gao, C., Liu, Y. et al. Monoubiquitination of filamin B regulates vascular endothelial growth factor-mediated trafficking of histone deacetylase 7 Mol. Cell. Biol., 33 (2013),pp. 1546-1560
[53]	Takafuta, T., Saeki, M., Fujimoto, T.T. et al. A new member of the LIM protein family binds to filamin B and localizes at stress fibers J. Biol. Chem., 278 (2003),pp. 12175-12181
[54]	Takafuta, T., Wu, G., Murphy, G.F. et al. Human beta-filamin is a new protein that interacts with the cytoplasmic tail of glycoprotein Ibalpha J. Biol. Chem., 273 (1998),pp. 17531-17538
[55]	Tenconi, R., Kozlowski, K., Largaiolli, G. Boomerang dysplasia. A new form of neonatal death dwarfism Rofo, 138 (1983),pp. 378-380
[56]	van der Flier, A., Kuikman, I., Kramer, D. et al. Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin (beta) subunits J. Cell Biol., 156 (2002),pp. 361-376
[57]	Wang, K., Ash, J.F., Singer, S.J. Filamin, a new high-molecular-weight protein found in smooth muscle and non-muscle cells Proc. Natl. Acad. Sci. U. S. A., 72 (1975),pp. 4483-4486
[58]	Wilson, S.G., Jones, M.R., Mullin, B.H. et al. J. Bone Min. Res., 24 (2009),pp. 1989-1997
[59]	Yang, H., Zheng, Z., Cai, H. et al. Hum. Genet., 135 (2016),pp. 1181-1189
[60]	Yang, S., Andras, L.M., Redding, G.J. et al. Early-onset scoliosis: a review of history, current treatment, and future directions Pediatrics, 137 (2016)
[61]	Zhao, Y., Shapiro, S.S., Eto, M. Am. J. Physiol. Cell Physiol., 310 (2016),pp. C89-C98
[62]	Zheng, L., Baek, H.J., Karsenty, G. et al. Filamin B represses chondrocyte hypertrophy in a Runx2/Smad3-dependent manner J. Cell Biol., 178 (2007),pp. 121-128
[63]	Zhou, A.X., Hartwig, J.H., Akyurek, L.M. Filamins in cell signaling, transcription and organ development Trends Cell Biol., 20 (2010),pp. 113-123
[64]	Zhou, X., Tian, F., Sandzen, J. et al. Filamin B deficiency in mice results in skeletal malformations and impaired microvascular development Proc. Natl. Acad. Sci. U. S. A., 104 (2007),pp. 3919-3924
[65]	Zieba, J., Forlenza, K.N., Khatra, J.S. et al. TGFβ and BMP dependent cell fate changes due to loss of Filamin B produces disc degeneration and progressive vertebral fusions PLoS Genet., 12 (2016),p. e1005936
[66]	Zieba, J., Zhang, W., Chong, J.X. et al. A postnatal role for embryonic myosin revealed by MYH3 mutations that alter TGFβ signaling and cause autosomal dominant spondylocarpotarsal synostosis Sci. Rep., 7 (2017),p. 41803