Osteoblasts synthesize and respond to transforming growth factor-type beta (TGF-beta) in vitro.

Abstract

Abstract. Transforming growth factor-type 13 has been identified as a constituent of bone matrix 261:5693-5695). We used both developing bone and bone-forming cells in vitro to demonstrate the cellular origin of this peptide. TGF-13 mRNA was detected by Northern analysis in both developing bone tissue and fetal bovine bone-forming cells using human cDNA probes. TGF-13 was shown to be synthesized and secreted by metabolically labeled bone cell cultures by immunoprecipitation from the medium. Further, TGF-13 activity was demonstrated in conditioned media from these cultures by competitive radioreceptor and growth promotion assays. Fetal bovine bone cells (FBBC) were found to have relatively few TGF-~ receptors (5,800/ce11) with an extremely low Kd of 2.2 pM (high binding affinity). In contrast to its inhibitory effects on the growth of many cell types including osteosarcoma cell lines, TGF-I3 stimulated the growth of subconfluent cultures of FBBC; it had little effect on the production of collagen by these cells. We conclude that bone-forming cells are a source for the TGF-I~ that is found in bone, and that these cells may be modulated by this factor in an autocrine fashion. TRANSFORMING growth factor-type 13 (TGF-13), ~ discovered and named for its ability to phenotypically transform nonneoplastic fibroblasts in vitro (30), is emerging as the prototype for a family of multifunctional regulatory peptides (38). Many cells, both nonneoplastic and neoplastic, synthesize TGF-13 and most of these cells have receptors for the peptide. The diverse effects of TGF-[~ on cell function have been further illuminated by the recent finding that TGF-[i is similar, if not identical, to cartilageinducing factor-A (36), a protein isolated from demineralized bone that induces the formation of cartilage proteoglycan and type II collagen from undifferentiated mesenchymal cells in vitro (35). Although platelets are the most concentrated source of TGF-13 in the body (2), the high yield of TGF-I~ from bone (14) (,,ol00-fold greater than from soft tissues such as placenta [10] and kidney [32]) suggests that bone has the greatest total amount of TGF-13. Since the level of serum-derived proteins in bone is high (e.g., ¢t2 HSglycoprotein, which is synthesized in the liver, can account for >2 % of the total bone matrix [40]), the origin of TGF-13 found in bone is not entirely clear, and some of it may simply be absorbed to the tissue from serum. Although recent studies of the production of growth factors by fetal rat calvaria have demonstrated secretion of TGF-13 into bone organ culture medium (5), this developing tissue contains both Abbreviations used in thispaper:FBBC, fetal bovine bone cells; TGF-I~, transforming growth factor-type 13; NRK, normal rat kidney fibroblasts. mineralized and nonmineralized regions, with ceils in nonmineralized regions exhibiting distinctly fibroblastic characteristics (i.e., production of types I and III collagen). Consequently, the cellular origin of TGF-I~ in this organ culture system also is unclear. In th...

Transforming Growth Factor β Suppresses Osteoblast Differentiation via the Vimentin Activating Transcription Factor 4 (ATF4) Axis

“…In the mammalian skeleton, TGF␤ is one of the most abundant cytokines stored in bone matrix; and once activated from its latent form, it promotes osteoblast proliferation and mesenchymal stem cell recruitment to active bone remodeling sites (1)(2)(3)(4)(5), while inhibits osteoblast differentiation (6 -8). The canonical Smad-dependent signaling has been identified as a mediator of TGF␤ in skeletal cells as well as in many other cell types.…”

Osteoblasts can induce dental pulp stem cells to undergo osteogenic differentiation

“…Fetal bovine bone cells are reported to transcribe TGF-b mRNA, and synthesize and secrete this peptide. As early as 1987, researchers confirmed that bone cells can be stimulated by TGF-b (Robey et al 1987). BMPs promote DPSCs osteogenesis by playing a pivotal role in endochondral bone formation Lavery et al 2008).…”

Plateletten Zengi̇n Plazma Ve Büyüme Faktörleri̇ni̇n Kemi̇k İyi̇leşmesi̇ Üzeri̇ne Olan Etki̇leri̇

“…Bu otolog plazma zengin bir büyüme faktörü kaynağıdır ve çeşitli uygulamalarının doku onarımı ve rejenerasyonunu arttırmada etkili bir yol olduğu gösterilmistir. [11][12][13] Plateletler yaralanmış damarlara fibrinojen vasıtasıyla yapıştıklarında, pıhtılaşma işlemini başlatmak amacıyla seratonin, tromboksan ve adenozin içeren granüller salgılamaya başlarlar. Daha sonra bu çözülmez ağdan yara yerine doğru plateletler aralarında PDGF, TGF-ß ve IGF'nin en önemlileri olduğu bir dizi büyüme faktörünü salgılarlar.…”

“…TGF-ß'nın prokollojen oluşturmak amacıyla fibroblastları uyarmasıyla yara bölgesinin içinde kollajen birikmeye başlar. 12 Bir çalışmada, platelet membranlarının insan trabeküler kemik hücrelerinin mitojenik aktivitelerini arttırdığı ve bu sayede mineralize dokuların rejenerasyonuna katkıda bulunduğu gösterilmistir. 13 İn vivo olarak gerçekleştirilen bir çalışmada ise Aghaloo 14 ve arkadaşları tavsan kafataslarında hazırladıkları 8 mm'lik defektleri otojen kemik, yalnız basına PRP ve otojen kemik-PRP kombinasyonu ile greftlemişler, kontrol grubuna ise herhangi bir tedavi uygulamamışlardır.…”

“…6,8,9,12,13 PRP'nin Bilesenleri PRP ile ilgili bugüne kadar yapılmış olan çalışmalar PRP içindeki plateletlerin granüllerinde basta PDGF, TGF-ß1, TGF--ß2 olmak üzere pek çok önemli büyüme faktörü bulunduğunu, bunun yanında IGF-I'in de periferal kandaki plateletlerde mevcut olduğunu göstermiştir. 6,8,9,12,13,[15][16][17][18][19][20][21][22][23][24][25][26][27] Platelet Derived Growth Factor (PGDF): Plateletlerin büyüme faktörü deposu olması ve hemostazda da rol oynuyor olmaları nedeniyle PDGF hemen hemen bütün yara iyileşme mekanizmalarında yer alır. Plateletlerin bu çok önemli çift fonksiyon özelliğinin muhtemelen bir hayatta kalma mekanizması olarak geliştiği düşünülmektedir.…”