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Versican and ADAMTSs are involved in bone development
International Congress Series 1284 (2005) 336 – 337
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Versican and ADAMTSs are involved in bone development M. Nakamura a,b,*, I. Takahashi c, S. Echigo a, Y. Sasano b a
Division of Oral Surgery, Tohoku University Graduate School of Dentistry, Japan b Division of Craniofacial Development and Regeneration, Tohoku University Graduate School of Dentistry, Japan c Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Japan
Abstract. ADAMTSs (a disintegrin and metalloprotease with thrombospondin type 1 motifs) constitute a family of extracellular proteases which are implicated in cleaving the protein versican. The process of bone development was divided into the beginning of osteogenesis, woven bone, and lamellar bone stages. Versican protein was abundant in the woven bone matrix, but decreased in the lamellar bone matrix. Versican mRNA was prominent in some osteoblasts with corresponding localization of the cognate protein. The temporal and spatial mRNA expression pattern of ADAMTS1, 4, and 5 was comparable with that of versican. These results suggest that woven bone rich in versican alters into lamellar bone containing little versican during bone development in both mandibles and hind limbs, where some osteoblasts may be involved in production as well as degradation of versican, by secreting ADAMTS1, 4, and 5. D 2005 Elsevier B.V. All rights reserved. Keywords: Versican; ADAMTS; Bone; Development; Extracellular matrix
1. Introduction The extracellular matrix (ECM) remodeling is achieved by both production and degradation of ECM molecules during bone development [1,2]. ADAMTS (a disintegrin and metalloprotease with thrombospondin type 1 motifs) is a family of extracellular proteases. ADAMTS1, 4, and 5 are known as proteases responsible for cleaving aggrecan, which is a major proteoglycan in cartilage [3–5]. These ADAMTSs are also reported to
* Corresponding author. Division of Oral Surgery, Tohoku University Graduate School of Dentistry, Japan. Tel.: +81 22 717 8395; fax: +81 22 717 8399. E-mail address: [email protected] (M. Nakamura). 0531-5131/ D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2005.06.015
M. Nakamura et al. / International Congress Series 1284 (2005) 336–337
337
degrade versican, which is a large chondroitin sulfate proteoglycan [6–8]. We hypothesized that versican is expressed in bone and its putative degrading enzymes ADAMTS1, 4, and 5 are also expressed and involved in versican remodeling during bone development. 2. Materials and methods Rat mandibles and hind limbs from day 14 postcoitum through week 6 postnatum were examined. The mRNA expression of versican, aggrecan, and ADAMTS1, 4, and 5 was localized by in situ hybridization. The distribution of versican protein was demonstrated by immunohistochemistry. 3. Results and discussion The process of bone development was divided into three stages, i.e. the beginning of osteogenesis, woven bone, and lamellar bone. The immunohistochemistry indicated that versican protein is abundant in the woven bone matrix, but decreases in the lamellar bone matrix. Versican mRNA was prominent in a certain population of osteoblasts, flat osteoblasts, with corresponding localization of the cognate protein. The temporal and spatial expression of ADAMTS1, 4, and 5 was comparable with one another and their expression pattern was similar to that of versican. Flat osteoblasts expressing versican and ADAMTS1, 4, and 5 intensely were recognized specifically in woven bone. In contrast, endostear osteoblasts with varied morphology and osteocytes expressed these molecules to some extent in lamellar bone. The mRNA expression of aggrecan was hardly identified in bone. These results suggest that versican is a distinctive component in bone, and woven bone rich in versican alters into lamellar bone containing little versican during development in both mandibles and hind limbs, where osteoblasts may be involved in both production and degradation of versican in the process by secreting ADAMTS1, 4, and 5.
References [1] Y. Sasano, et al., Gene expression of MMP8 and MMP13 during embryonic development of bone and cartilage in the rat mandible and hind limb, J. Histochem. Cytochem. 50 (2002) 325 – 3325. [2] N. Ortega, et al., How proteases regulate bone morphogenesis, Ann. N.Y. Acad. Sci. 995 (2003) 109 – 116. [3] M.D. Tortorella, et al., Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins, Science 284 (1999) 1664 – 1666. [4] I. Abbaszade, et al., Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family, J. Biol. Chem. 274 (1999) 23443 – 23450. [5] K. Kuno, et al., ADAMTS-1 cleaves a cartilage proteoglycan, aggrecan, FEBS Lett. 478 (2000) 241 – 245. [6] J.D. Sandy, et al., Versican V1 proteolysis in human aorta in vivo occurs at the Glu441–Ala442 bond, a site that is cleaved by recombinant ADAMTS-1 and ADAMTS-4, J. Biol. Chem. 276 (2001) 13372 – 13378. [7] D.L. Russell, et al., Processing and localization of ADAMTS-1 and proteolytic cleavage of versican during cumulus matrix expansion and ovulation, J. Biol. Chem. 278 (2003) 42330 – 42339. [8] J. Westling, et al., ADAMTS4 (aggrecanase-1) cleaves human brain versican V2 at Glu405–Gln406 to generate glial hyaluronate binding protein, Biochem. J. 377 (2004) 787 – 795.
www.ics-elsevier.com
Versican and ADAMTSs are involved in bone development M. Nakamura a,b,*, I. Takahashi c, S. Echigo a, Y. Sasano b a
Division of Oral Surgery, Tohoku University Graduate School of Dentistry, Japan b Division of Craniofacial Development and Regeneration, Tohoku University Graduate School of Dentistry, Japan c Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Japan
Abstract. ADAMTSs (a disintegrin and metalloprotease with thrombospondin type 1 motifs) constitute a family of extracellular proteases which are implicated in cleaving the protein versican. The process of bone development was divided into the beginning of osteogenesis, woven bone, and lamellar bone stages. Versican protein was abundant in the woven bone matrix, but decreased in the lamellar bone matrix. Versican mRNA was prominent in some osteoblasts with corresponding localization of the cognate protein. The temporal and spatial mRNA expression pattern of ADAMTS1, 4, and 5 was comparable with that of versican. These results suggest that woven bone rich in versican alters into lamellar bone containing little versican during bone development in both mandibles and hind limbs, where some osteoblasts may be involved in production as well as degradation of versican, by secreting ADAMTS1, 4, and 5. D 2005 Elsevier B.V. All rights reserved. Keywords: Versican; ADAMTS; Bone; Development; Extracellular matrix
1. Introduction The extracellular matrix (ECM) remodeling is achieved by both production and degradation of ECM molecules during bone development [1,2]. ADAMTS (a disintegrin and metalloprotease with thrombospondin type 1 motifs) is a family of extracellular proteases. ADAMTS1, 4, and 5 are known as proteases responsible for cleaving aggrecan, which is a major proteoglycan in cartilage [3–5]. These ADAMTSs are also reported to
* Corresponding author. Division of Oral Surgery, Tohoku University Graduate School of Dentistry, Japan. Tel.: +81 22 717 8395; fax: +81 22 717 8399. E-mail address: [email protected] (M. Nakamura). 0531-5131/ D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2005.06.015
M. Nakamura et al. / International Congress Series 1284 (2005) 336–337
337
degrade versican, which is a large chondroitin sulfate proteoglycan [6–8]. We hypothesized that versican is expressed in bone and its putative degrading enzymes ADAMTS1, 4, and 5 are also expressed and involved in versican remodeling during bone development. 2. Materials and methods Rat mandibles and hind limbs from day 14 postcoitum through week 6 postnatum were examined. The mRNA expression of versican, aggrecan, and ADAMTS1, 4, and 5 was localized by in situ hybridization. The distribution of versican protein was demonstrated by immunohistochemistry. 3. Results and discussion The process of bone development was divided into three stages, i.e. the beginning of osteogenesis, woven bone, and lamellar bone. The immunohistochemistry indicated that versican protein is abundant in the woven bone matrix, but decreases in the lamellar bone matrix. Versican mRNA was prominent in a certain population of osteoblasts, flat osteoblasts, with corresponding localization of the cognate protein. The temporal and spatial expression of ADAMTS1, 4, and 5 was comparable with one another and their expression pattern was similar to that of versican. Flat osteoblasts expressing versican and ADAMTS1, 4, and 5 intensely were recognized specifically in woven bone. In contrast, endostear osteoblasts with varied morphology and osteocytes expressed these molecules to some extent in lamellar bone. The mRNA expression of aggrecan was hardly identified in bone. These results suggest that versican is a distinctive component in bone, and woven bone rich in versican alters into lamellar bone containing little versican during development in both mandibles and hind limbs, where osteoblasts may be involved in both production and degradation of versican in the process by secreting ADAMTS1, 4, and 5.
References [1] Y. Sasano, et al., Gene expression of MMP8 and MMP13 during embryonic development of bone and cartilage in the rat mandible and hind limb, J. Histochem. Cytochem. 50 (2002) 325 – 3325. [2] N. Ortega, et al., How proteases regulate bone morphogenesis, Ann. N.Y. Acad. Sci. 995 (2003) 109 – 116. [3] M.D. Tortorella, et al., Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins, Science 284 (1999) 1664 – 1666. [4] I. Abbaszade, et al., Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family, J. Biol. Chem. 274 (1999) 23443 – 23450. [5] K. Kuno, et al., ADAMTS-1 cleaves a cartilage proteoglycan, aggrecan, FEBS Lett. 478 (2000) 241 – 245. [6] J.D. Sandy, et al., Versican V1 proteolysis in human aorta in vivo occurs at the Glu441–Ala442 bond, a site that is cleaved by recombinant ADAMTS-1 and ADAMTS-4, J. Biol. Chem. 276 (2001) 13372 – 13378. [7] D.L. Russell, et al., Processing and localization of ADAMTS-1 and proteolytic cleavage of versican during cumulus matrix expansion and ovulation, J. Biol. Chem. 278 (2003) 42330 – 42339. [8] J. Westling, et al., ADAMTS4 (aggrecanase-1) cleaves human brain versican V2 at Glu405–Gln406 to generate glial hyaluronate binding protein, Biochem. J. 377 (2004) 787 – 795.