The Cooperative Effect of Genistein and Protein Hydrolysates on the Proliferation and Survival of Osteoblastic Cells (hFOB 1.19)

Abstract

Chum salmon skin gelatin, de-isoflavoned soy protein, and casein were hydrolyzed at two degrees of hydrolysis. Genistein, the prepared hydrolysates, and genistein-hydrolysate combinations were assessed for their proliferative and anti-apoptotic effects on human osteoblasts (hFOB 1.19) to clarify potential cooperative effects between genistein and these hydrolysates in these two activities. Genistein at 2.5 µg/L demonstrated the highest proliferative activity, while the higher dose of genistein inhibited cell growth. All hydrolysates promoted osteoblast proliferation by increasing cell viability to 102.9%-131.1%. Regarding etoposide-or NaF-induced osteoblast apoptosis, these hydrolysates at 0.05 g/L showed both preventive and therapeutic effects against apoptosis. In the mode of apoptotic prevention, the hydrolysates decreased apoptotic cells from 32.9% to 15.2%-23.7% (etoposide treatment) or from 23.6% to 14.3%-19.6% (NaF treatment). In the mode of apoptotic rescue, the hydrolysates lessened the extent of apoptotic cells from 15.9% to 13.0%-15.3% (etoposide treatment) or from 13.3% to 10.9%-12.7% (NaF treatment). Gelatin hydrolysates showed the highest activities among all hydrolysates in all cases. All investigated combinations (especially the genistein-gelatin hydrolysate combination) had stronger proliferation, apoptotic prevention, and rescue than genistein itself or their counterpart hydrolysates alone, suggesting that genistein cooperated with these hydrolysates, rendering greater activities in osteoblast proliferation and anti-apoptosis.

Genistein contributes to cell cycle progression and regulates oxidative stress in primary culture of osteoblasts along with osteoclasts attenuation

“…The elongated and fusiform morphology of osteoblasts suggested the features of bone cell proliferation. This result is consistent with some previous reports where GS induced cell proliferation in primary mouse bone marrow-derived mesenchymal stem cells and human osteoblast cell line hFOB 1.19 [26,27]. Alkaline phosphatase enzyme plays an essential role in the mineralization of osteoblasts and, thus, matrix mineralization is the vital process in bone formation.…”

The Growth Proliferation, Apoptotic Prevention, and Differentiation Induction of the Gelatin Hydrolysates from Three Sources to Human Fetal Osteoblasts (hFOB 1.19 Cells)

“…However, the present results did not support that the hydrolysates with relative higher 4-Hyp contents exerted better activities. The assessed hydrolysates in this study with higher DH values always had higher activities, which was consistent with the previous results [ 20 , 32 , 39 ]. It was mostly found in this study that the papain-generated hydrolysates had higher activities than the osteoblasts ( Table 2 , Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 and Figure 6 ).…”

“…Furthermore, estrogen receptor can stimulate a Src/Shc/ERK signaling pathway that prevents apoptosis induced by dexamethasone, EP, and other pro-apoptotic agents [ 31 ]. Several protein hydrolysates such as that from chum salmon skin gelatin have been verified with apoptotic prevention, decreasing total apoptotic proportion from 23.6–32.9% to 14.3–15.2% in NaF- or EP-induced apoptosis [ 32 ]. In this study, both cisplatin- and EP-induced osteoblast apoptosis were conducted, while the assessed hydrolysates all had apoptotic prevention on the osteoblasts via decreasing total apoptotic proportions significantly ( p < 0.05, Figure 1 , Figure 2 and Figure 3 ).…”

Molekularne mechanizmy działania genisteiny w świetle terapii chorób genetycznych i immunologicznych

“…Niektóre wyniki badań pokazują, że może ona działać mutagennie [15], chociaż inne doniesienia wskazują na jej anty-mutagenne właściwości [16]. W warunkach laboratoryjnych zaobserwowano również jej aktywność w hamowaniu proliferacji komórek [17]. Efekt ten, podobnie jak efekty genotoksyczne, również zależny jest od użytego stężenia izoflawonu [18], natomiast wartym wspomnienia jest fakt, że roczna eksperymentalna terapia genisteiną z udziałem dzieci w dawce 150 mg/kg/dzień, co jest niezwykle wysoką dawką, nie wykazała żadnych efektów niepożądanych [19].…”