A gene expression profile for endochondral bone formation: oligonucleotide microarrays establish novel connections between known genes and BMP-2-induced bone formation in mouse quadriceps

Clancy, Brian M.; Johnson, Joyce D; Lambert, Andre Jean; Rezvankhah, Saeid; Wong, Anthony; Resmini, Christine; Feldman, Jeffrey L.; Leppanen, Scott; Pittman, Debra D.

doi:10.1016/s8756-3282(03)00116-9

Cited by 67 publications

(43 citation statements)

References 58 publications

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“…hand, BMP-2 treatment of murine C2C12 premyoblastic cells has been observed to elevate Wnt inhibitory factor-1 [Vaes et al, 2002] and sFRP-2 [Vaes et al, 2002;Balint et al, 2003] messages, while treatment of mouse muscle in vivo with BMP-2 was reported to increase sFRP-1, -2, -3 and -4 as well as FZD-1 mRNAs [Clancy et al, 2003]. BMP-2 has also been observed to up-regulate Wnt-1, -3a, -5b, -7, -9b as well as FZD-1 and -9 mRNA expression in murine pluripotent mesenchymal cell lines and MC-3T3-E1 osteoblastic cells; in addition, it increases Tcf-1 and Lef-1 message levels, but suppresses low-density lipoprotein receptorrelated protein (LRP)-1, LRP-5 and sFRP-2 mRNA expression in MC-3T3-E1 cells .…”

Section: Discussionmentioning

confidence: 95%

“…The results are presented as mean AE SD, n ¼ 6, *P < 0.001 versus the vehicle control cells. Clancy et al, 2003] have also discovered new potential mechanisms for the bone anabolic actions of these agents. Among the important new signaling pathways that have been revealed by these studies is the Wnt pathway [de Jong et al, 2002;Doi et al, 2002;Harris and Harris, 2002;Vaes et al, 2002;Balint et al, 2003;Clancy et al, 2003;Qi et al, 2003;RomanRoman et al, 2003;Westendorf et al, 2004].…”

Section: Discussionmentioning

confidence: 99%

“…Clancy et al, 2003] have also discovered new potential mechanisms for the bone anabolic actions of these agents. Among the important new signaling pathways that have been revealed by these studies is the Wnt pathway [de Jong et al, 2002;Doi et al, 2002;Harris and Harris, 2002;Vaes et al, 2002;Balint et al, 2003;Clancy et al, 2003;Qi et al, 2003;RomanRoman et al, 2003;Westendorf et al, 2004]. For example, treatment of UMR-106 rat osteosarcoma cells with PTH has been reported to upregulate sFRP-4 mRNA expression [Qin et al, 2003], and to increase Frizzled (FZD)-1 and -2 mRNA levels [Chan et al, 1992].…”

Section: Discussionmentioning

confidence: 99%

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The Wnt antagonist secreted frizzled‐related protein‐1 controls osteoblast and osteocyte apoptosis

Bodine¹,

Billiard²,

Moran³

et al. 2005

J of Cellular Biochemistry

157

113

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Mechanisms controlling human bone formation remain to be fully elucidated. We have used differential display-polymerase chain reaction analysis to characterize osteogenic pathways in conditionally immortalized human osteoblasts (HOBs) representing distinct stages of differentiation. We identified 82 differentially expressed messages and found that the Wnt antagonist secreted frizzled-related protein (sFRP)-1 was the most highly regulated of these. Transient transfection of HOBs with sFRP-1 suppressed canonical Wnt signaling by 70% confirming its antagonistic function in these cells. Basal sFRP-1 mRNA levels increased 24-fold during HOB differentiation from pre-osteoblasts to pre-osteocytes, and then declined in mature osteocytes. This expression pattern correlated with levels of cellular viability such that the preosteocytes, which had the highest levels of sFRP-1 mRNA, also had the highest rate of cell death. Basal sFRP-1 mRNA levels also increased 29-fold when primary human mesenchymal stem cells were differentiated to osteoblasts supporting the developmental regulation of the gene. Expression of sFRP-1 mRNA was induced 38-fold following prostaglandin E 2 (PGE 2 ) treatment of pre-osteoblasts and mature osteoblasts that had low basal message levels. In contrast, sFRP-1 expression was down-regulated by as much as 80% following transforming growth factor (TGF)-b1 treatment of preosteocytes that had high basal mRNA levels. Consistent with this, treatment of pre-osteoblasts and mature osteoblasts with PGE 2 increased apoptosis threefold, while treatment of pre-osteocytes with TGF-b1 decreased cell death by 50%. Likewise, over-expression of sFRP-1 in HOBs accelerated the rate of cell death threefold. These results establish sFRP-1 as an important negative regulator of human osteoblast and osteocyte survival.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Wnt antagonist secreted frizzled‐related protein‐1 controls osteoblast and osteocyte apoptosis

Bodine¹,

Billiard²,

Moran³

et al. 2005

J of Cellular Biochemistry

157

113

View full text Add to dashboard Cite

show abstract

“…The physiologic substrates and functions of MMP-23 are unknown, but gelatinolytic activity has been demonstrated, an activity that could be inhibited by both synthetic inhibitors and TIMPs 1 and 2 (51,52). The level of MMP-23 mRNA was observed to peak during an experimentally induced endochondral bone formation, with both osteoblasts and chondrocytes expressing the gene (53). Since fibrocartilagenous transformation and endochondral ossification Compared with the normal tendon group, the levels of TIMP-3 mRNA were lower in the painful tendon group.…”

Section: Discussionmentioning

confidence: 99%

Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon

Jones¹,

Corps²,

Pennington³

et al. 2006

Arthritis & Rheumatism

261

284

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Objective. To profile the messenger RNA (mRNA) expression for the 23 known genes of matrix metalloproteinases (MMPs), 19 genes of ADAMTS, 4 genes of tissue inhibitors of metalloproteinases (TIMPs), and ADAM genes 8, 10, 12, and 17 in normal, painful, and ruptured Achilles tendons.Methods. Tendon samples were obtained from cadavers or from patients undergoing surgical procedures to treat chronic painful tendinopathy or ruptured tendon. Total RNA was extracted and mRNA expression was analyzed by quantitative real-time reverse transcription-polymerase chain reaction, normalized to 18S ribosomal RNA.Results. In comparing expression of all genes, the normal, painful, and ruptured Achilles tendon groups each had a distinct mRNA expression signature. Three mRNA were not detected and 14 showed no significant difference in expression levels between the groups. Statistically significant (P < 0.05) differences in mRNA expression, when adjusted for age, included lower levels of MMPs 3 and 10 and TIMP-3 and higher levels of ADAM-12 and MMP-23 in painful compared with normal tendons, and lower levels of MMPs 3 and 7 and TIMPs 2, 3, and 4 and higher levels of ADAMs 8 and 12, MMPs 1, 9, 19, and 25, and TIMP-1 in ruptured compared with normal tendons.Conclusion. The distinct mRNA profile of each tendon group suggests differences in extracellular proteolytic activity, which would affect the production and remodeling of the tendon extracellular matrix. Some proteolytic activities are implicated in the maintenance of normal tendon, while chronically painful tendons and ruptured tendons are shown to be distinct groups. These data will provide a foundation for further study of the role and activity of many of these enzymes that underlie the pathologic processes in the tendon.

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“…70 MMP23A and -B are expressed in numerous tissues, including placenta, ovary, testis, prostate, heart, and pancreas. 69,70 In addition, using gene expression analysis of hBMP2 injected in vivo into mouse quadriceps to induce bone formation, Clancy et al 31 showed increased expression of Mmp23 in osteoblasts and chrondrocytes, suggesting a role for Mmp23 in bone formation and remodeling.…”

Section: Mechanisms For Generating Complex Rearrangements Of Chromosomentioning

confidence: 99%

Delineation of mechanisms and regions of dosage imbalance in complex rearrangements of 1p36 leads to a putative gene for regulation of cranial suture closure

Gajęcka

Ballif

et al. 2004

Eur J Hum Genet

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Structural chromosome abnormalities have aided in gene identification for over three decades. Delineation of the deletion sizes and rearrangements allows for phenotype/genotype correlations and ultimately assists in gene identification. In this report, we have delineated the precise rearrangements in four subjects with deletions, duplications, and/or triplications of 1p36 and compared the regions of imbalance to two cases recently published. Fluorescence in situ hybridization (FISH) analysis revealed the size, order, and orientation of the duplicated/triplicated segments in each subject. We propose a premeiotic model for the formation of these complex rearrangements in the four newly ascertained subjects, whereby a deleted chromosome 1 undergoes a combination of multiple breakage-fusion-bridge (BFB) cycles and inversions to produce a chromosome arm with a complex rearrangement of deleted, duplicated and triplicated segments. In addition, comparing the six subjects' rearrangements revealed a region of overlap that when triplicated is associated with craniosynostosis and when deleted is associated with large, late-closing anterior fontanels. Within this region are the MMP23A and -B genes. We show MMP23 gene expression at the cranial sutures and we propose that haploinsufficiency results in large, late-closing anterior fontanels and overexpression results in craniosynostosis. These data emphasize the important role of cytogenetics in investigating and uncovering the etiologies of human genetic disease, particularly cytogenetic imbalances that reveal potentially dosage-sensitive genes.

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A gene expression profile for endochondral bone formation: oligonucleotide microarrays establish novel connections between known genes and BMP-2-induced bone formation in mouse quadriceps

Cited by 67 publications

References 58 publications

The Wnt antagonist secreted frizzled‐related protein‐1 controls osteoblast and osteocyte apoptosis

The Wnt antagonist secreted frizzled‐related protein‐1 controls osteoblast and osteocyte apoptosis

Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon

Delineation of mechanisms and regions of dosage imbalance in complex rearrangements of 1p36 leads to a putative gene for regulation of cranial suture closure

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