Transforming growth factor‐beta 1 (TGF‐β1) prevents the age‐dependent decrease in bone formation in human osteoblast/implant cultures

Abstract

Titanium implants have been extensively used in orthopedic surgery and dentistry. Most of the patients who receive such implants are elderly with a compromised ability to heal and form new bone. By using an in vitro osteoblast/implant culture system, the potency of TGF-beta1 in enhancing mineralization of human osteoblast cultures from elderly subjects was investigated in this study. Primary human osteoblast (HOB) cells obtained from different age group human subjects [Young (Y), Middle (M), and Old (O)] were cultured on Ti alloy (Ti-6Al-4V) disks with or without continuous administration of 0.2 ng/mL TGF-beta1 in the medium for 2 or 4 weeks. TGF-beta1 significantly (p < 0.05) increased calcium content and the size of calcified nodules on implant disks in the O group, but had no effect on the Y or M groups. The number of calcified nodules was not different with or without TGF-beta1 in all age groups. As measured by Northern blot analysis and RT-PCR, TGF-beta1 significantly increased the expression of bone-specific extracellular matrix proteins, including alkaline phosphatase, Type I collagen, bone sialoprotein and osteocalcin, after both 2 and 4 weeks in the O group but not in the Y group. In conclusion, TGF-beta1 enhances mineralization on implant materials of osteoblast cultures from elderly human subjects.

Effects of autogenous growth factors on heterotopic bone formation of osteogenic cells in small animal model

“…In this study positive effects of growth factor contents released from PC containing TGF-b1 ranging from 25 to 250 ng/ml (1e10 ng in 40 ml of PPP) on bone formation capacity of the rBMSC were not found. This was in contrast to dose dependent effects of growth factors derived from PC and TGF-b1 in vitro (Arpornmaeklong et al, 2004;Lieb et al, 2004;Zhang et al, 2005;Graziani et al, 2006;de Oliva et al, 2009). The negative results might be due to the insufficient concentrations and low osteogenic potency of soluble growth factors or osteoblastic differentiation stages of the transplanted rBMSC (Kasten et al, 2006).…”

Profiling Insulin Like Factor 3 (INSL3) Signaling in Human Osteoblasts

“…Osteopontin comprises about the 2% of the non-collagenous protein in bone [35] and it has important roles in bone turnover serving as attachment for osteoclasts activating the resorption cascade [36]. TGF-β is produced by osteoblasts and regulates the proliferation and differentiation of osteoblasts both in vitro and in vivo [37] by regulating the production of different genes such as those of the bone specific extracellular matrix proteins including type I collagen [38]. INSL3 could therefore have an important role in matrix deposition as it stimulates the expression of genes coding for collagenous and non–collagenous proteins.…”

Mechanism of Mineralization of Collagen‐Based Connective Tissues

“…In osteoblast cultures, TGF 1, which is the most abundant growth factor in bone, also stimulates proteoglycan synthesis [257], bone sialoprotein synthesis [258] and has no effect on osteonectin synthesis [258]. Although TGF 1 stimulates the formation of an HA nucleator (bone sialoprotein), it has been reported in mouse osteoblast-like cultures, to inhibit alkaline phosphatase activity and mineralization [259], while on implant surfaces it enhances mineralization [260]. Some of these variations in effect may be related to cell age and to dosage.…”