Primary Cilia Are Necessary for Prx1-expressing Cells to Contribute to Postnatal Skeletogenesis

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2018 Jul 14

PMID 30002136

Citations 20

Authors

Emily R Moore

Yuchen Yang

Christopher R Jacobs

Affiliations

Soon will be listed here.

Abstract

Although Prx1 (also known as PRRX1)-expressing cells and their primary cilia are critical for embryonic development, they have yet to be studied in the context of postnatal skeletogenesis owing to the lethality of mouse models. A tamoxifen-inducible Prx1 model has been developed, and we determined that expression directed by this promoter is highly restricted to the cambium layers in the periosteum and perichondrium after birth. To determine the postnatal role of these cambium layer osteochondroprogenitors (CLOPs) and their primary cilia, we developed models to track the fate of CLOPs (Prx1CreER-GFP;Rosa26) and selectively disrupt their cilia (Prx1CreER-GFP;Ift88). Our tracking studies revealed that CLOPs populate cortical and trabecular bone, the growth plate and secondary ossification centers during the normal program of postnatal skeletogenesis. Furthermore, animals lacking CLOP cilia exhibit stunted limb growth due to disruptions in endochondral and intramembranous ossification. Histological examination indicates that growth is stunted due to limited differentiation, proliferation and/or abnormal hypertrophic differentiation in the growth plate. Collectively, our results suggest that CLOPs are programmed to rapidly populate distant tissues and produce bone via a primary cilium-mediated mechanism in the postnatal skeleton.

Citing Articles

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A periosteum-derived cell line to study the role of BMP/TGFβ signaling in periosteal cell behavior and function.

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Primary cilia support cartilage regeneration after injury.

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References

RICHMAN C, Kutilek S, Miyakoshi N, Srivastava A, Beamer W, Donahue L . Postnatal and pubertal skeletal changes contribute predominantly to the differences in peak bone density between C3H/HeJ and C57BL/6J mice. J Bone Miner Res. 2001; 16(2):386-97. DOI: 10.1359/jbmr.2001.16.2.386. View

Alvarez J, Sohn P, Zeng X, Doetschman T, Robbins D, Serra R . TGFbeta2 mediates the effects of hedgehog on hypertrophic differentiation and PTHrP expression. Development. 2002; 129(8):1913-24. DOI: 10.1242/dev.129.8.1913. View

Lui J, Nilsson O, Baron J . Growth plate senescence and catch-up growth. Endocr Dev. 2011; 21:23-29. PMC: 3420820. DOI: 10.1159/000328117. View

Lamon S, Zacharewicz E, Butchart L, Orellana L, Mikovic J, Grounds M . MicroRNA expression patterns in post-natal mouse skeletal muscle development. BMC Genomics. 2017; 18(1):52. PMC: 5219731. DOI: 10.1186/s12864-016-3399-2. View

Wu L, Lu M, Genge B, Guo G, Nie D, Wuthier R . Discovery of sonic hedgehog expression in postnatal growth plate chondrocytes: differential regulation of sonic and Indian hedgehog by retinoic acid. J Cell Biochem. 2002; 87(2):173-87. DOI: 10.1002/jcb.10285. View

Logan M, Martin J, Nagy A, Lobe C, Olson E, Tabin C . Expression of Cre Recombinase in the developing mouse limb bud driven by a Prxl enhancer. Genesis. 2002; 33(2):77-80. DOI: 10.1002/gene.10092. View

Walzer S, Cetin E, Grubl-Barabas R, Sulzbacher I, Rueger B, Girsch W . Vascularization of primary and secondary ossification centres in the human growth plate. BMC Dev Biol. 2014; 14:36. PMC: 4236517. DOI: 10.1186/s12861-014-0036-7. View

White R, Bierinx A, Gnocchi V, Zammit P . Dynamics of muscle fibre growth during postnatal mouse development. BMC Dev Biol. 2010; 10:21. PMC: 2836990. DOI: 10.1186/1471-213X-10-21. View

Houben A, Kostanova-Poliakova D, Weissenbock M, Graf J, Teufel S, von der Mark K . β-catenin activity in late hypertrophic chondrocytes locally orchestrates osteoblastogenesis and osteoclastogenesis. Development. 2016; 143(20):3826-3838. PMC: 5087647. DOI: 10.1242/dev.137489. View

10.

Ferretti C, Mattioli-Belmonte M . Periosteum derived stem cells for regenerative medicine proposals: Boosting current knowledge. World J Stem Cells. 2014; 6(3):266-77. PMC: 4131269. DOI: 10.4252/wjsc.v6.i3.266. View

11.

Oni O . Osteocalcin expression in the groove of Ranvier of the rabbit growth plate. Injury. 1997; 28(2):109-11. DOI: 10.1016/s0020-1383(96)00172-6. View

12.

Ascenzi M, Blanco C, Drayer I, Kim H, Wilson R, Retting K . Effect of localization, length and orientation of chondrocytic primary cilium on murine growth plate organization. J Theor Biol. 2011; 285(1):147-55. PMC: 3163056. DOI: 10.1016/j.jtbi.2011.06.016. View

13.

Song B, Haycraft C, Seo H, Yoder B, Serra R . Development of the post-natal growth plate requires intraflagellar transport proteins. Dev Biol. 2007; 305(1):202-16. PMC: 1931410. DOI: 10.1016/j.ydbio.2007.02.003. View

14.

Ascenzi M, Lenox M, Farnum C . Analysis of the orientation of primary cilia in growth plate cartilage: a mathematical method based on multiphoton microscopical images. J Struct Biol. 2007; 158(3):293-306. PMC: 2040051. DOI: 10.1016/j.jsb.2006.11.004. View

15.

Takarada T, Nakazato R, Tsuchikane A, Fujikawa K, Iezaki T, Yoneda Y . Genetic analysis of Runx2 function during intramembranous ossification. Development. 2015; 143(2):211-8. DOI: 10.1242/dev.128793. View

16.

Li Y, Dudley A . Noncanonical frizzled signaling regulates cell polarity of growth plate chondrocytes. Development. 2009; 136(7):1083-92. PMC: 2685929. DOI: 10.1242/dev.023820. View

17.

Bashur L, Chen D, Chen Z, Liang B, Pardi R, Murakami S . Loss of jab1 in osteochondral progenitor cells severely impairs embryonic limb development in mice. J Cell Physiol. 2014; 229(11):1607-17. PMC: 4157318. DOI: 10.1002/jcp.24602. View

18.

Kanno T, Takahashi T, Ariyoshi W, Tsujisawa T, Haga M, Nishihara T . Tensile mechanical strain up-regulates Runx2 and osteogenic factor expression in human periosteal cells: implications for distraction osteogenesis. J Oral Maxillofac Surg. 2005; 63(4):499-504. DOI: 10.1016/j.joms.2004.07.023. View

19.

Goetz S, Anderson K . The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet. 2010; 11(5):331-44. PMC: 3121168. DOI: 10.1038/nrg2774. View

20.

Chang H, Knothe Tate M . Concise review: the periosteum: tapping into a reservoir of clinically useful progenitor cells. Stem Cells Transl Med. 2012; 1(6):480-91. PMC: 3659712. DOI: 10.5966/sctm.2011-0056. View