Systemic administration of transforming growth factor-beta 2 prevents the impaired bone formation and osteopenia induced by unloading in rats.

Machwate, Mohamed; Zérath, E.; Holy, Xavier; Hott, M.; Godet, Danielle; Lomri, Abderrahim; Marie, Pierre J.

doi:10.1172/jci118158

Cited by 69 publications

(45 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another bone growth factor that is a member of BMP family is transforming growth factor b (TGFb or TGFB1) that promotes osteoblastic cell proliferation, function, and survival (75). In vivo, TGFb does not prevent bone loss induced by ovariectomy (76) but prevents immobilization-related bone loss caused by decreased osteoblastogenesis (77,78). Inhibins (Inh), activins, and myostatins (GDF8) are other members of the TGFb superfamily that control bone metabolism (79).…”

Section: Growth Factorsmentioning

confidence: 99%

Osteoblasts in osteoporosis: past, emerging, and future anabolic targets

Marie¹,

Kassem²

2011

European Journal of Endocrinology

187

143

View full text Add to dashboard Cite

Objective: Age-related bone loss is associated with significant changes in bone remodeling characterized by decreased trabecular and periosteal bone formation relative to bone resorption, resulting in bone fragility and increased risk of fractures. Prevention or reversal of age-related decrease in bone mass and increase in bone fragility has been based on inhibition of bone resorption using anticatabolic drugs. The current challenge is to promote osteoblastogenesis and bone formation to prevent age-related bone deterioration. Methods: A limited number of approved therapeutic molecules are available to activate bone formation. Therefore, there is a need for anabolic drugs that promote bone matrix apposition at the endosteal, endocortical, and periosteal envelopes by increasing the number of osteoblast precursor cells and/or the function of mature osteoblasts. In this study, we review current therapeutics promoting bone formation and anabolic molecules targeting signaling pathways involved in osteoblastogenesis, based on selected full-text articles searched on Medline search from 1990 to 2010. Results and discussion: We present current therapeutic approaches focused on intermittent parathyroid hormone and Wnt signaling agonists/antagonists. We also discuss novel approaches for prevention and treatment of defective bone formation and bone loss associated with aging and osteoporosis. These strategies targeting osteoblastic cell functions may prove to be useful in promoting bone formation and improving bone strength in the aging population.

show abstract

Section: Growth Factorsmentioning

confidence: 99%

Osteoblasts in osteoporosis: past, emerging, and future anabolic targets

Marie¹,

Kassem²

2011

European Journal of Endocrinology

187

143

View full text Add to dashboard Cite

show abstract

“…Our observations are consistent with the substantial body of evidence implicating TGF-b in the regulation of osteoblast and osteoclast activity. However, most of the available data suggest that TGF-b activity promotes mineralization [5][6][7][8][9]11], and low levels might be expected in osteoporosis. This apparent paradox would be resolved if the serum concentration of TGF-b3 were inversely related to the TGF-b3 concentration in the bone tissue.…”

Section: Figmentioning

confidence: 99%

“…Evidence for the role of TGF-b in regulating bone mineral density (BMD) comes from a number of observations: it is present at high concentration in bone [3,4], it promotes osteoblast proliferation [5] and their subsequent differentiation [6], and also decreases osteoclast activity by several mechanisms [7,8]. The rate of bone formation is altered in TGF-b1 knockout mice [9], and administration of TGF-b corrects the bone density deficiency in elderly mice with osteoporosis [10] and in rats with suspension-induced osteoporosis [11]. Mutations in the gene encoding human TGF-b1 have also been associated with low BMD [12].…”

Section: Introductionmentioning

confidence: 99%

The Role of Serum TGF-β Isoforms as Potential Markers of Osteoporosis

Grainger

Percival

Chiano

et al. 1999

Osteoporosis International

View full text Add to dashboard Cite

Osteoporosis is a major public health problem characterized by low bone mineral density (BMD) that presently has no biochemical test useful for its diagnosis. The cytokine TGF-beta has been postulated to play a role in controlling bone density by regulating the fine balance between bone matrix deposition by osteoblasts and its resorption by osteoclasts. We explored whether measurement of serum levels of different TGF-beta isoforms could be useful as a clinical tool in osteoporosis. We measured the concentration of TGF-beta1 antigen using the BDA19 capture sandwich enzyme-linked immunosorbent assay (ELISA), TGF-beta2 antigen concentration using a Quantikine sandwich ELISA kit and TGF-beta3 antigen concentration using a modified version of the TGF-beta1 Quantikine sandwich ELISA kit. Subjects were 41 women with osteoporosis (with nontraumatic vertebral fracture or lumbar spine BMD Z-score <-1.5 SD) and a total of 199 control women from different sources. Serum concentrations of TGF-beta1 and TGF-beta2 were similar in all groups. However, detectable levels of TGF-beta3 (>0.2 ng/ml) were found in 35 of 41 patients with osteoporosis (median 7.2 (5.2-8.9) ng/ml) compared with 11 of 36 controls or 24 of 89 healthy women of unknown bone density. Differences among the groups could not be accounted for by age, weight, medications, use of hormone replacement therapy or the presence of osteoarthritis. Using the optimal cut-off of >/=2 ng/ml, the test was able to detect an individual with low spine BMD (Z-score <-1.5) with a sensitivity of 84% and a specificity of 53%, with similar results for the femoral neck. The odds ratio for osteoporosis associated with a positive test at this level was 5.93 (95% CI 2.41-11.59), and 4.1 (95% CI 1.66-10.11) using the WHO cut-off of T-score <-2.5. Serum TGF-beta3 concentration is raised in osteoporotic women and the test appears to have potential as a marker for osteoporosis. The underlying mechanisms and the relationships between TGF-beta3 and bone turnover and fractures remain to be explored.

show abstract

“…TGF P enhances collagen and noncollagen protein synthesis by the osteoblast and stimulates bone matrix apposition rates in calvarial cultures (Centrella et al, 1987;Hock et al, 1990). This stimulator effect is confirmed in vivo, and the local and systemic administration of TGF (1enhances bone formation (Machwate et al, 1995;Marcelli et al, 1990;Rosen et al, 1994). In addition to its stimulator effects on bone formation, TGF~might alter bone collagen degradation, an effect that could prove critical to the maintenance of bone matrix.…”

mentioning

confidence: 91%

Transforming growth factor β1 inhibits collagenase 3 expression by transcriptional and post-transcriptional mechanisms in osteoblast cultures

Rydziel¹,

Varghese²,

Canalis³

1997

J. Cell. Physiol.

View full text Add to dashboard Cite

Transforming growth factor (TGF) beta1 is an autocrine regulator of bone cell function. We demonstrated that TGF beta1 enhances bone collagen synthesis, but its effects on collagen degradation are not well characterized. We tested the effects of TGF beta1 on rat collagenase 3 expression in cultures of osteoblast-enriched cells from fetal rat calvariae (Ob cells). Treatment with TGF beta1 at 0.4 nM decreased steady state collagenase mRNA levels after 2 to 24 h. This dose-dependent effect was observed at TGF beta1 concentrations of 4 pM to 1.2 nM, and was accompanied by decreased levels of immunoreactive procollagenase. The protein synthesis inhibitor cycloheximide increased collagenase transcripts, but did not prevent the effect of TGF beta1 on collagenase mRNA levels. TGF beta1 accelerated the decay of collagenase mRNA in transcriptionally arrested Ob cells. In addition, TGF beta1 decreased the levels of collagenase heterogeneous nuclear RNA and the rate of collagenase gene transcription in Ob cells. TGF beta1 enhanced the expression of tissue inhibitors of metalloproteinases (TIMP) 1 and 3 and caused a modest decrease of TIMP 2 mRNA levels. In conclusion, TGF beta1 decreases interstitial collagenase transcripts and protease levels in Ob cells by transcriptional and post-transcriptional mechanisms, and this effect may contribute to its actions on bone matrix.

show abstract

Systemic administration of transforming growth factor-beta 2 prevents the impaired bone formation and osteopenia induced by unloading in rats.

Cited by 69 publications

References 67 publications

Osteoblasts in osteoporosis: past, emerging, and future anabolic targets

Osteoblasts in osteoporosis: past, emerging, and future anabolic targets

The Role of Serum TGF-β Isoforms as Potential Markers of Osteoporosis

Transforming growth factor β1 inhibits collagenase 3 expression by transcriptional and post-transcriptional mechanisms in osteoblast cultures

Contact Info

Product

Resources

About