Concentration of Transforming Growth Factor Beta in Human Bone Tissue: Relationship to Age, Menopause, Bone Turnover, and Bone Volume

Pfeilschifter, Johannes; Diel, Ingo J.; Scheppach, Beate; Bretz, A; Krempien, Robert; Erdmann, Johannes; Schmid, Gerald; Reske, Nicole; Bismar, H; Seck, Thomas; Krempien, B.; Ziegler, Reinhard

doi:10.1359/jbmr.1998.13.4.716

Cited by 85 publications

(65 citation statements)

References 23 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus one might speculate that, during the late steps of osteosynthesis such as the mineralization phase, the inhibitory effect of high concentrations of TGF-1 during bone remodelling could be suppressed, as lower levels of T Rs would enable mineralization in regions where the organic bone matrix is already sufficiently formed. The concentrations of active TGF-1 applied in our in vitro incubation experiments are unlikely to be supraphysiological, and are even lower than those reported recently for human bone tissue (Nicolas et al 1994, Pfeilschifter et al 1998. However, it cannot completely be ruled out that an activation of latent TGF-1 stored in the matrix occurred during the extraction procedure, which might have resulted in higher concentrations of detectable TGF-l when only active TGF-1 was measured.…”

Section: Discussioncontrasting

confidence: 55%

“…TGF-is secreted by bone cells and stored in the bone matrix in a latent form, ready to be activated and inactivated at key, pivotal stages in the process of bone formation . There is recent experimental evidence that activated TGF-can be extracted in substantial concentrations from the bone matrix (Pfeilschifter et al 1998). However, little is known about how the responsiveness of osteoblasts towards active TGF-present in the osteoblastic microenvironment might be regulated in humans, although adaptive changes of the responsiveness might represent further control mechanisms once TGF-is activated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ligand-induced downregulation of receptors for TGF-beta in human osteoblast-like cells from adult donors

Gebken

A²,

Brinckmann³

et al. 1999

Journal of Endocrinology

View full text Add to dashboard Cite

High concentrations of transforming growth factor b (TGF-) are found in the bone matrix, reflecting a pivotal role of this growth factor in the coupling of bone resorption and formation. TGF-strongly stimulates the synthesis of extracellular matrix proteins, but in vitro studies show an inhibitory effect on the final mineralization process, which in vivo occurs despite high concentrations of TGF-. Little is known about how bone-forming cells respond to different concentrations of TGF-and if they can transiently adapt receptor numbers in order to modulate cellular activity. Against this background, we studied the cell-surface expression of TGF-receptors (T R) I, II and III (betaglycan) on human osteoblast-like cells from adult donors, and examined the T R presentation on these cells after a preceding exposure to TGF-1. Affinity crosslinking studies with disuccinimidylsuberate showed the presence of all three receptor types. Preincubation with TGF-1 markedly reduced 125 I-TGF-1 binding in a time-dependent and dose-dependent manner and revealed a 95% reduction after an 18-h preincubation with 200 pM TGF-1. In parallel, Scatchard analysis showed that the binding affinity did not change as a consequence of TGF-1 preincubation. Immunoblotting analyses revealed an almost complete disappearance of immunoreactive T R-II and T R-III proteins after a 24-h preincubation with TGF-1. Using semi-quantitative reverse transcription PCR, no effect of TGF-1 on the expression of T R-II mRNA was observed. These studies demonstrate a ligand-induced downregulation of T Rs-II and -III on human osteoblast-like cells, without any evidence for recovery within the first 24 h, both in the presence and after the removal of the ligand. The underlying mechanism appears to be based on post-transcriptional events. The results suggest that high concentrations of active TGF-1 decrease the responsiveness of osteoblasts towards this growth factor.

show abstract

Section: Discussioncontrasting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Ligand-induced downregulation of receptors for TGF-beta in human osteoblast-like cells from adult donors

Gebken

A²,

Brinckmann³

et al. 1999

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…TGF-␤1 is concentrated in mineralized human bone but declines in concentration with age, and levels in bone matrix correlate with bone turnover rates (15). The release and activation of TGF-␤1 by osteoclasts in bone matrix has been implicated in several sequential steps in bone remodeling: recruitment of osteoblast precursor cells, induction of matrix deposition, and mineralization.…”

mentioning

confidence: 99%

Regulation of Osteogenesis by Fetuin

Binkert¹,

Demetriou²,

Sukhu³

et al. 1999

Journal of Biological Chemistry

118

View full text Add to dashboard Cite

Osteoporosis is a common problem of aging and results from a failure of homeostatic mechanisms to regulate osteogenesis and mineralization. Bovine and human forms of fetuin glycoprotein bind to the transforming growth factor (TGF)-␤/BMP (bone morphogenic protein) cytokines and block their osteogenic activity in cell culture assays (Demetriou, M., Binkert, C., Sukhu, B., Tenenbaum, H. C., and Dennis, J. W. (1996) J. Biol. Chem. 271, 12755-12761). Fetuin is a prominent serum glycoprotein and a major noncollagenous component of mineralized bone in mammals. In this study, we show that recombinant fetuin and native serum protein have similar potency as inhibitors of osteogenesis in dexamethasone-treated rat bone marrow cell cultures (dex-RBMC). Recombinant bovine fetuin also bound to TGF-␤1 and BMP-2 in vitro with kinetics similar to native fetuin. Although TGF-␤1 is required for osteogenesis in dex-RBMC, the cytokine also inhibited osteogenesis at concentrations >10 pM. Titration of fetuin or anti-TGF-␤1 antibodies into the bone marrow cultures in the presence of 10 pM TGF-␤1 restored osteogenesis, whereas titrations of the same reagents into cultures with 0.3 pM added TGF-␤1 were inhibitory, confirming the biphasic nature of the TGF-␤1 response. Suppression of osteogenesis by both TGF-␤1 and the antagonist proteins required their presence within the first 6 days of culture, well before mineralization at 10 -12 days. Northern analysis showed that both fetuin and high dose TGF-␤1 suppressed expression of the bone-associated transcripts alkaline phosphatase, osteopontin, collagen type I, and bone sialoprotein. The suppression of osteogenesis by fetuin and by high dose TGF-␤1 was accompanied by the differentiation of an alternate cell lineage with adipocyte characteristics. In summary, the biphasic osteogenic response to TGF-␤1 suggests that overlapping gradients of TGF-␤/BMP cytokines and fetuin regulate osteogenesis in remodeling bone.

show abstract

“…This limited access to biochemical factors during a healing response contributes to the already weakened healing response in older patients. Some evidence exists that the growth factor levels within bone matrix also decline with age [54,59]. S103 Table 1 Basic principles for enhancement of bone healing and bone formation and their mechanisms Osteoporosis Osteoporosis leads to a decrease in bone volume, especially in areas with trabecular bone tissue.…”

Section: Agementioning

confidence: 99%

Factors stimulating bone formation

Lind¹,

Bünger²

2002

The Use of Bone Substitutes in Spine Surgery

View full text Add to dashboard Cite

IntroductionOsseous spinal fusion remains a cornerstone of surgical treatment of severe spinal disorders. However, the success rate is still debated and difficult to assess in the presence of metal implant material. A general failure rate of 5-30% is reported in lumbar spinal fusion [58]. Fusion capacity is influenced by numerous factors: individual biological factors, the bone graft material, and biomechanical and external factors. Predictive factors for good osseous fusion are uniformly associated with good functional outcome, for which psychosocial factors, the presence of neurodeficit, and the primary diagnosis also seem to have major importance.The individual biological factors governing spinal fusion are related to bone homeostasis and thereby to age. Little is known about individual variations in spinal fusion capacity, although it is generally accepted that young patients heal well. Recent studies have shown that all osteotropic growth factors known to be sequentially involved in the spinal fusion process [6] are present in iliac crest bone autografts of all age groups but with higher variation in older people [3, 16]. Other growth factors that regulate vascular ingrowth have not been addressed and might be equally important. Osteotropic growth factors such as TGF β, BMP2, and BMP7 have been shown experimentally to induce/provide sufficient bone formation for both intracorporal and posterolateral spinal fusion at the level of bone autografts in sheep, rabbits, and baboons [9, 22], but the clinical effectiveness has yet to be determined in controlled studies and negative and positive results have been reported [7, 38,39]. At present, the cost effectiveness of osteotropic growth factors for humans seems very high compared to combined femoral ring allograft and autograft for anterior interbody fusion or to morselized human allograft in posterolateral fusion.Bone autograft harvesting is associated with high donor site morbidity (15-20%), even in long-term follow-up. Limited amounts of material are available in osteoporotic patients and for multilevel procedures. Bone cement, structural bone allograft, and metal spacers are viable alternaAbstract The aim of this review is to describe major approaches for stimulating bone healing and to review other factors affecting bone healing. Spinal bone fusion after surgery is a demanding process requiring optimal conditions for clinical success. Bone formation and healing can be enhanced through various methods. Experimental studies have revealed an array of stimulative measures. These include biochemical stimulation by use of hormones and growth factors, physical stimulation through mechanical and electromagnetic measures, and bone grafting by use of bone tissue or bone substitutes. Newer biological techniques such as stem cell transplantation and gene therapy can also be used to stimulate bone healing. Apart from bone transplantation, clinical experience with the many stimulation modalities is limited. Possible areas for clinical use of these novel methods are discu...

show abstract

Concentration of Transforming Growth Factor Beta in Human Bone Tissue: Relationship to Age, Menopause, Bone Turnover, and Bone Volume

Cited by 85 publications

References 23 publications

Ligand-induced downregulation of receptors for TGF-beta in human osteoblast-like cells from adult donors

Ligand-induced downregulation of receptors for TGF-beta in human osteoblast-like cells from adult donors

Regulation of Osteogenesis by Fetuin

Factors stimulating bone formation

Contact Info

Product

Resources

About