Tags

Type your tag names separated by a space and hit enter

Hedgehog-Gli activators direct osteo-chondrogenic function of bone morphogenetic protein toward osteogenesis in the perichondrium.
J Biol Chem. 2013 Apr 05; 288(14):9924-32.JB

Abstract

Specification of progenitors into the osteoblast lineage is an essential event for skeletogenesis. During endochondral ossification, cells in the perichondrium give rise to osteoblast precursors. Hedgehog (Hh) and bone morphogenetic protein (BMP) are suggested to regulate the commitment of these cells. However, properties of perichondrial cells and regulatory mechanisms of the specification process are still poorly understood. Here, we investigated the machineries by combining a novel organ culture system and single-cell expression analysis with mouse genetics and biochemical analyses. In a metatarsal organ culture reproducing bone collar formation, activation of BMP signaling enhanced the bone collar formation cooperatively with Hh input, whereas the signaling induced ectopic chondrocyte formation in the perichondrium without Hh input. Similar phenotypes were also observed in compound mutant mice, where signaling activities of Hh and BMP were genetically manipulated. Single-cell quantitative RT-PCR analyses showed heterogeneity of perichondrial cells in terms of natural characteristics and responsiveness to Hh input. In vitro analyses revealed that Hh signaling suppressed BMP-induced chondrogenic differentiation; Gli1 inhibited the expression of Sox5, Sox6, and Sox9 (SRY box-containing gene 9) as well as transactivation by Sox9. Indeed, ectopic expression of chondrocyte maker genes were observed in the perichondrium of metatarsals in Gli1(-/-) fetuses, and the phenotype was more severe in Gli1(-/-);Gli2(-/-) newborns. These data suggest that Hh-Gli activators alter the function of BMP to specify perichondrial cells into osteoblasts; the timing of Hh input and its target populations are critical for BMP function.

Authors+Show Affiliations

Center for Disease Biology and Integrative Medicine, The University of Tokyo, Tokyo 113-0033, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23423383

Citation

Hojo, Hironori, et al. "Hedgehog-Gli Activators Direct Osteo-chondrogenic Function of Bone Morphogenetic Protein Toward Osteogenesis in the Perichondrium." The Journal of Biological Chemistry, vol. 288, no. 14, 2013, pp. 9924-32.
Hojo H, Ohba S, Taniguchi K, et al. Hedgehog-Gli activators direct osteo-chondrogenic function of bone morphogenetic protein toward osteogenesis in the perichondrium. J Biol Chem. 2013;288(14):9924-32.
Hojo, H., Ohba, S., Taniguchi, K., Shirai, M., Yano, F., Saito, T., Ikeda, T., Nakajima, K., Komiyama, Y., Nakagata, N., Suzuki, K., Mishina, Y., Yamada, M., Konno, T., Takato, T., Kawaguchi, H., Kambara, H., & Chung, U. I. (2013). Hedgehog-Gli activators direct osteo-chondrogenic function of bone morphogenetic protein toward osteogenesis in the perichondrium. The Journal of Biological Chemistry, 288(14), 9924-32. https://doi.org/10.1074/jbc.M112.409342
Hojo H, et al. Hedgehog-Gli Activators Direct Osteo-chondrogenic Function of Bone Morphogenetic Protein Toward Osteogenesis in the Perichondrium. J Biol Chem. 2013 Apr 5;288(14):9924-32. PubMed PMID: 23423383.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hedgehog-Gli activators direct osteo-chondrogenic function of bone morphogenetic protein toward osteogenesis in the perichondrium. AU - Hojo,Hironori, AU - Ohba,Shinsuke, AU - Taniguchi,Kiyomi, AU - Shirai,Masataka, AU - Yano,Fumiko, AU - Saito,Taku, AU - Ikeda,Toshiyuki, AU - Nakajima,Keiji, AU - Komiyama,Yuske, AU - Nakagata,Naomi, AU - Suzuki,Kentaro, AU - Mishina,Yuji, AU - Yamada,Masahisa, AU - Konno,Tomohiro, AU - Takato,Tsuyoshi, AU - Kawaguchi,Hiroshi, AU - Kambara,Hideki, AU - Chung,Ung-il, Y1 - 2013/02/19/ PY - 2013/2/21/entrez PY - 2013/2/21/pubmed PY - 2013/6/1/medline SP - 9924 EP - 32 JF - The Journal of biological chemistry JO - J Biol Chem VL - 288 IS - 14 N2 - Specification of progenitors into the osteoblast lineage is an essential event for skeletogenesis. During endochondral ossification, cells in the perichondrium give rise to osteoblast precursors. Hedgehog (Hh) and bone morphogenetic protein (BMP) are suggested to regulate the commitment of these cells. However, properties of perichondrial cells and regulatory mechanisms of the specification process are still poorly understood. Here, we investigated the machineries by combining a novel organ culture system and single-cell expression analysis with mouse genetics and biochemical analyses. In a metatarsal organ culture reproducing bone collar formation, activation of BMP signaling enhanced the bone collar formation cooperatively with Hh input, whereas the signaling induced ectopic chondrocyte formation in the perichondrium without Hh input. Similar phenotypes were also observed in compound mutant mice, where signaling activities of Hh and BMP were genetically manipulated. Single-cell quantitative RT-PCR analyses showed heterogeneity of perichondrial cells in terms of natural characteristics and responsiveness to Hh input. In vitro analyses revealed that Hh signaling suppressed BMP-induced chondrogenic differentiation; Gli1 inhibited the expression of Sox5, Sox6, and Sox9 (SRY box-containing gene 9) as well as transactivation by Sox9. Indeed, ectopic expression of chondrocyte maker genes were observed in the perichondrium of metatarsals in Gli1(-/-) fetuses, and the phenotype was more severe in Gli1(-/-);Gli2(-/-) newborns. These data suggest that Hh-Gli activators alter the function of BMP to specify perichondrial cells into osteoblasts; the timing of Hh input and its target populations are critical for BMP function. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/23423383/Hedgehog_Gli_activators_direct_osteo_chondrogenic_function_of_bone_morphogenetic_protein_toward_osteogenesis_in_the_perichondrium_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)67353-7 DB - PRIME DP - Unbound Medicine ER -