Mice lacking Bmp6 function

Solloway, Mark J.; Dudley, Andrew T.; Bikoff, Elizabeth K.; Lyons, Karen M.; Hogan, Brigid L.M.; Robertson, Elizabeth

doi:10.1002/(sici)1520-6408(1998)22:4<321::aid-dvg3>3.3.co;2-7

Cited by 136 publications

(171 citation statements)

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“…The results suggest that the response of ADAS cells to known chondrogenic agents differs considerably from the response of other mesenchyme-derived progenitor cells, such as MSCs. Notably, and in contrast to the osteogenic effects of BMP-6 on many cell types (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49), the effects of BMP-6 on ADAS cells in 3-D culture are highly chondrogenic, and among the growth factors investigated in this study, BMP-6 was shown to be the most potent regulator of chondrogenesis.…”

Section: Discussionmentioning

confidence: 63%

Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6

Estes

Guilak

2006

Arthritis & Rheumatism

271

212

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Objective. Recent studies have identified an abundant source of multipotent progenitor cells in subcutaneous human adipose tissue, termed human adiposederived adult stem cells (ADAS cells). In response to specific media formulations, including transforming growth factor ␤1 (TGF␤1), these cells exhibit significant ability to differentiate into a chondrocyte-like phenotype, expressing cartilage-specific genes and proteins such as aggrecan and type II collagen. However, the influence of other growth factors on the chondrogenic differentiation of ADAS cells is not fully understood. This study was undertaken to investigate the effects of TGF␤1, TGF␤3, insulin-like growth factor 1, bone morphogenetic protein 6 (BMP-6), and dexamethasone, in various combinations, on the chondrogenic potential of ADAS cells in alginate beads.Methods. The chondrogenic response of alginateencapsulated ADAS cells was measured by quantitative polymerase chain reaction, 3 H-proline and 35 S-sulfate incorporation, and immunolabeling for specific extracellular matrix components.Results. Significant differences in chondrogenesis were observed under the different culture conditions for all outcomes measured. Most notably, BMP-6 upregulated AGC1 and COL2A1 expression by an average of 205-fold and 38-fold, respectively, over day-0 controls, while down-regulating COL10A1 expression by ϳ2-fold.Conclusion. These findings suggest that BMP-6 is a potent inducer of chondrogenesis in ADAS cells, in contrast to mesenchymal stem cells, which exhibit increased expression of type X collagen and a hypertrophic phenotype in response to BMP-6. Combinations of growth factors containing BMP-6 may provide a novel means of regulating the differentiation of ADAS cells for applications in the tissue-engineered repair or regeneration of articular cartilage.

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Section: Discussionmentioning

confidence: 63%

Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6

Estes

Guilak

2006

Arthritis & Rheumatism

271

212

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“…74 Its expression during embryogenesis is closely coupled with BMP-2, and the lack of noticeable defects in BMP-6-deficient mice may be due to functional compensation by BMP-2. 74 Nevertheless, our findings corroborate well with a recent study in which BMP-6 was shown to induce the most rapid tissue calcification when compared with BMP-2 or BMP-4 in an athymic nude rat model, 75 although for reasons to be determined AdBMP-4 reproducibly failed to induce orthotopic bone formation in this study. BMP-9 is one of the least studied members of the BMP family.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

et al. 2004

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Efficacious bone regeneration could revolutionize the clinical management of bone and musculoskeletal disorders. Although several bone morphogenetic proteins (BMPs) (mostly BMP-2 and BMP-7) have been shown to induce bone formation, it is unclear whether the currently used BMPs represent the most osteogenic ones. Until recently, comprehensive analysis of osteogenic activity of all BMPs has been hampered by the fact that recombinant proteins are either not biologically active or not available for all BMPs. In this study, we used recombinant adenoviruses expressing the 14 types of BMPs (AdBMPs), and demonstrated that, in addition to currently used BMP-2 and BMP-7, BMP-6 and BMP-9 effectively induced orthotopic ossification when either AdBMP-transduced osteoblast progenitors or the viral vectors were injected into the quadriceps of athymic mice. Radiographic and histological evaluation demonstrated that BMP-6 and BMP-9 induced the most robust and mature ossification at multiple time points. BMP-3, a negative regulator of bone formation, was shown to effectively inhibit orthotopic ossification induced by BMP-2, BMP-6, and BMP-7. However, BMP-3 exerted no inhibitory effect on BMP-9-induced bone formation, suggesting that BMP-9 may transduce osteogenic signaling differently. Our findings suggest that BMP-6 and BMP-9 may represent more effective osteogenic factors for bone regeneration.

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“…On the other hand, Bmp6 Ϫ/Ϫ animals survive to adulthood (Solloway et al, 1998), with no apparent fertility phenotype, despite the expression of Bmp6 in the neonatal testis (www.ncbi.gov/geo/GDS2098, GDS401, GDS605). BMP6 may be dispensable or alternatively, other BMPs may compensate for the loss of BMP6 by activating SMAD proteins to sufficient levels to induce expression of BMP6 target Diagrammatic representation of Smad1,5,8,Smad4, and Smad6 and 7 mRNA expression during adult mouse spermatogenesis based on the data described in this study.…”

Section: Discussionmentioning

confidence: 99%

SMAD expression in the testis: An insight into BMP regulation of spermatogenesis

Itman

Loveland

2007

Developmental Dynamics

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Bone morphogenetic proteins (BMPs), members of the transforming growth factor-␤ superfamily, extensively influence events that establish male fertility, affecting germ cells and somatic cells throughout fetal and postnatal life. BMP signals are relayed by SMAD proteins, transcription factors that translocate to the nucleus upon ligand stimulation. We show that BMP signaling in the testis may be regulated by selective expression of BMP-responsive and inhibitory SMADs, with expression differing between the first wave and adult spermatogenesis. Smad1, Smad5, Smad8, Smad4, Smad6, and Smad7 expression is ubiquitous during testis development but becomes cell-specific in the adult. Furthermore, regulated SMAD6 protein expression at the onset of spermatogenesis suggests differential responsiveness of spermatogonial subpopulations to ligands. In vitro, immature Sertoli cells and spermatogonia transduce BMP2 and BMP4 signals by means of SMAD1, SMAD5, and SMAD8. Based on these findings, we extrapolate these data to interpret BMP mutant testis phenotypes in terms of SMAD availability for signal transduction. Developmental Dynamics 237:97-111, 2008.

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Mice lacking Bmp6 function

Cited by 136 publications

References 0 publications

Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6

Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6

Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery

SMAD expression in the testis: An insight into BMP regulation of spermatogenesis

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