A role for N-cadherin in the development of the differentiated osteoblastic phenotype

S L Ferrari; K Traianedes; M Thorne; M H Lafage-Proust; P Genever; M G Cecchini; V Behar; A Bisello; M Chorev; M Rosenblatt; L J Suva

A role for N-cadherin in the development of the differentiated osteoblastic phenotype

S L Ferrari, K Traianedes, M Thorne, M H Lafage-Proust, P Genever, M G Cecchini, V Behar, A Bisello, M Chorev, M Rosenblatt, L J Suva

Biology

Research output: Contribution to journal › Article › peer-review

Abstract

Cadherins are a family of cell surface adhesion molecules that play an important role in tissue differentiation. A limited repertoire of cadherins has been identified in osteoblasts, and the role of these molecules in osteoblast function remains to be elucidated. We recently cloned an osteoblast-derived N-cadherin gene from a rat osteoblast complementary DNA library. After in situ hybridization of rat bone and immunohistochemistry of human osteophytes, N-cadherin expression was localized prominently in well-differentiated (lining) osteoblasts, Northern blot hybridization in primary cultures of fetal rat calvaria and in human SaOS-2 and rat ROS osteoblast-like cells showed a relationship between N-cadherin messenger RNA expression and cell-to-cell adhesion, morphological differentiation, and alkaline phosphatase and osteocalcin gene expression. Treatment with a synthetic peptide containing the His-Ala-Val (HAV) adhesion motif of N-cadherin significantly decreased bone nodule formation in primary cultures of fetal rat calvaria and inhibited cell-to-cell contact in rat osteoblastic TRAB-11 cells. HAV peptide also regulated the expression of specific genes such as alkaline phosphatase and the immediate early gene zif268 in SaOS-2 cells. Transient transfection of SaOS-2 cells with a dominant-negative N-cadherin mutant (NCAD Delta C) significantly inhibited their morphological differentiation. In addition, aggregation of NCTC cells derived from mouse connective tissue stably transfected with osteoblast-derived N-cadherin was inhibited by either treatment with HAV or transfection with NCAD Delta C. Together, these results strongly support a role for N-cadherin, in concert with other previously identified osteoblast cadherins, in the late stages of osteoblast differentiation.

Original language	English
Pages (from-to)	198-208
Number of pages	11
Journal	JOURNAL OF BONE AND MINERAL RESEARCH
Volume	15
Issue number	2
Publication status	Published - Feb 2000

Keywords

N-cadherin
osteoblast
differentiation
adhesion
dominant-negative
RAT OSTEO-SARCOMA
PARATHYROID-HORMONE
INTERCELLULAR COMMUNICATION
GENE-EXPRESSION
CELL-ADHESION
BIMOLECULAR INTERACTIONS
PROTEIN-RECEPTOR
NETWORKS
CLONING
CONTACT

Cite this

@article{56c184194c7c4b6b9f3f02965aee1647,

title = "A role for N-cadherin in the development of the differentiated osteoblastic phenotype",

abstract = "Cadherins are a family of cell surface adhesion molecules that play an important role in tissue differentiation. A limited repertoire of cadherins has been identified in osteoblasts, and the role of these molecules in osteoblast function remains to be elucidated. We recently cloned an osteoblast-derived N-cadherin gene from a rat osteoblast complementary DNA library. After in situ hybridization of rat bone and immunohistochemistry of human osteophytes, N-cadherin expression was localized prominently in well-differentiated (lining) osteoblasts, Northern blot hybridization in primary cultures of fetal rat calvaria and in human SaOS-2 and rat ROS osteoblast-like cells showed a relationship between N-cadherin messenger RNA expression and cell-to-cell adhesion, morphological differentiation, and alkaline phosphatase and osteocalcin gene expression. Treatment with a synthetic peptide containing the His-Ala-Val (HAV) adhesion motif of N-cadherin significantly decreased bone nodule formation in primary cultures of fetal rat calvaria and inhibited cell-to-cell contact in rat osteoblastic TRAB-11 cells. HAV peptide also regulated the expression of specific genes such as alkaline phosphatase and the immediate early gene zif268 in SaOS-2 cells. Transient transfection of SaOS-2 cells with a dominant-negative N-cadherin mutant (NCAD Delta C) significantly inhibited their morphological differentiation. In addition, aggregation of NCTC cells derived from mouse connective tissue stably transfected with osteoblast-derived N-cadherin was inhibited by either treatment with HAV or transfection with NCAD Delta C. Together, these results strongly support a role for N-cadherin, in concert with other previously identified osteoblast cadherins, in the late stages of osteoblast differentiation.",

keywords = "N-cadherin, osteoblast, differentiation, adhesion, dominant-negative, RAT OSTEO-SARCOMA, PARATHYROID-HORMONE, INTERCELLULAR COMMUNICATION, GENE-EXPRESSION, CELL-ADHESION, BIMOLECULAR INTERACTIONS, PROTEIN-RECEPTOR, NETWORKS, CLONING, CONTACT",

author = "Ferrari, {S L} and K Traianedes and M Thorne and Lafage-Proust, {M H} and P Genever and Cecchini, {M G} and V Behar and A Bisello and M Chorev and M Rosenblatt and Suva, {L J}",

year = "2000",

month = feb,

language = "English",

volume = "15",

pages = "198--208",

journal = "JOURNAL OF BONE AND MINERAL RESEARCH",

issn = "0884-0431",

publisher = "Wiley-Blackwell",

number = "2",

}

TY - JOUR

T1 - A role for N-cadherin in the development of the differentiated osteoblastic phenotype

AU - Ferrari, S L

AU - Traianedes, K

AU - Thorne, M

AU - Lafage-Proust, M H

AU - Genever, P

AU - Cecchini, M G

AU - Behar, V

AU - Bisello, A

AU - Chorev, M

AU - Rosenblatt, M

AU - Suva, L J

PY - 2000/2

Y1 - 2000/2

N2 - Cadherins are a family of cell surface adhesion molecules that play an important role in tissue differentiation. A limited repertoire of cadherins has been identified in osteoblasts, and the role of these molecules in osteoblast function remains to be elucidated. We recently cloned an osteoblast-derived N-cadherin gene from a rat osteoblast complementary DNA library. After in situ hybridization of rat bone and immunohistochemistry of human osteophytes, N-cadherin expression was localized prominently in well-differentiated (lining) osteoblasts, Northern blot hybridization in primary cultures of fetal rat calvaria and in human SaOS-2 and rat ROS osteoblast-like cells showed a relationship between N-cadherin messenger RNA expression and cell-to-cell adhesion, morphological differentiation, and alkaline phosphatase and osteocalcin gene expression. Treatment with a synthetic peptide containing the His-Ala-Val (HAV) adhesion motif of N-cadherin significantly decreased bone nodule formation in primary cultures of fetal rat calvaria and inhibited cell-to-cell contact in rat osteoblastic TRAB-11 cells. HAV peptide also regulated the expression of specific genes such as alkaline phosphatase and the immediate early gene zif268 in SaOS-2 cells. Transient transfection of SaOS-2 cells with a dominant-negative N-cadherin mutant (NCAD Delta C) significantly inhibited their morphological differentiation. In addition, aggregation of NCTC cells derived from mouse connective tissue stably transfected with osteoblast-derived N-cadherin was inhibited by either treatment with HAV or transfection with NCAD Delta C. Together, these results strongly support a role for N-cadherin, in concert with other previously identified osteoblast cadherins, in the late stages of osteoblast differentiation.

AB - Cadherins are a family of cell surface adhesion molecules that play an important role in tissue differentiation. A limited repertoire of cadherins has been identified in osteoblasts, and the role of these molecules in osteoblast function remains to be elucidated. We recently cloned an osteoblast-derived N-cadherin gene from a rat osteoblast complementary DNA library. After in situ hybridization of rat bone and immunohistochemistry of human osteophytes, N-cadherin expression was localized prominently in well-differentiated (lining) osteoblasts, Northern blot hybridization in primary cultures of fetal rat calvaria and in human SaOS-2 and rat ROS osteoblast-like cells showed a relationship between N-cadherin messenger RNA expression and cell-to-cell adhesion, morphological differentiation, and alkaline phosphatase and osteocalcin gene expression. Treatment with a synthetic peptide containing the His-Ala-Val (HAV) adhesion motif of N-cadherin significantly decreased bone nodule formation in primary cultures of fetal rat calvaria and inhibited cell-to-cell contact in rat osteoblastic TRAB-11 cells. HAV peptide also regulated the expression of specific genes such as alkaline phosphatase and the immediate early gene zif268 in SaOS-2 cells. Transient transfection of SaOS-2 cells with a dominant-negative N-cadherin mutant (NCAD Delta C) significantly inhibited their morphological differentiation. In addition, aggregation of NCTC cells derived from mouse connective tissue stably transfected with osteoblast-derived N-cadherin was inhibited by either treatment with HAV or transfection with NCAD Delta C. Together, these results strongly support a role for N-cadherin, in concert with other previously identified osteoblast cadherins, in the late stages of osteoblast differentiation.

KW - N-cadherin

KW - osteoblast

KW - differentiation

KW - adhesion

KW - dominant-negative

KW - RAT OSTEO-SARCOMA

KW - PARATHYROID-HORMONE

KW - INTERCELLULAR COMMUNICATION

KW - GENE-EXPRESSION

KW - CELL-ADHESION

KW - BIMOLECULAR INTERACTIONS

KW - PROTEIN-RECEPTOR

KW - NETWORKS

KW - CLONING

KW - CONTACT

M3 - Article

SN - 0884-0431

VL - 15

SP - 198

EP - 208

JO - JOURNAL OF BONE AND MINERAL RESEARCH

JF - JOURNAL OF BONE AND MINERAL RESEARCH

IS - 2

ER -