TY - JOUR
T1 - Osteoclast differentiation is downregulated by select polyphenolic fractions from dried plum via suppression of MAPKs and Nfatc1 in mouse C57BL/6 primary bone marrow cells
AU - Graef, Jennifer L.
AU - Rendina-Ruedy, Elizabeth
AU - Crockett, Erica K.
AU - Ouyang, Ping
AU - Wu, Lei
AU - King, Jarrod B.
AU - Cichewicz, Robert H.
AU - Lin, Dingbo
AU - Lucas, Edralin A.
AU - Smith, Brenda J.
N1 - Publisher Copyright:
© 2017, Graef et al.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Background: Clinical and preclinical studies have shown that dietary supplementation with dried plum improves bone health. These osteoprotective effects are a result, in part, of the antiresorptive properties of the fruit, which appear to be mediated by its polyphenolic compounds. Objective: This study was designed to determine if certain fractions of the polyphenolic compounds in dried plums are responsible for the antiresorptive effects and whether they alter mitogen-activated protein kinase (MAPK) and calcium signaling, which are essential to osteoclast differentiation and activity, under normal and inflammatory conditions. Methods: Six polyphenolic fractions were derived from the total polyphenolic extract of dried plum based on solubility. Initial screening, with the use of the Raw 264.7 monocyte and macrophage cell line, showed that 3 fractions had the most marked capacity to downregulate osteoclast differentiation. This response was confirmed in 2 of the fractions by using primary bone marrow-derived cultures and in all subsequent experiments to determine how osteoclast differentiation and function were altered with a focus on these 2 fractions in primary cultures. Data were analyzed by using ANOVA followed by post hoc analyses. Results: Both of the polyphenol fractions decreased osteoclast differentiation and activity coincident with downregulating nuclear factor of activated T cells, cytoplasmic, calcineurindependent 1 (Nfatc1), which is required for osteoclast differentiation. Calcium signaling, essential for the auto-amplification of Nfatc1, was suppressed by the polyphenolic fractions under normal conditions as indicated by suppressed mRNA expression of costimulatory receptors osteoclastassociated receptor (Oscar), signaling regulatory protein β1 (Sirpb1), and triggering receptor expressed on myeloid cells 2 (Trem2). In contrast, in the presence of tumor necrosis factor α (TNF-α), only Sirpb1 was downregulated. In addition to calcium signaling, phosphorylation of extracellular signal-regulated kinase (Erk) and p38 MAPK, involved in the expression and activation of Nfatc1, was also suppressed by the polyphenolic fractions. Conclusion: These results show that certain types of polyphenolic compounds from dried plum downregulate calcium and MAPK signaling, resulting in suppression of Nfatc1 expression, which ultimately decreases osteoclast formation and activity.
AB - Background: Clinical and preclinical studies have shown that dietary supplementation with dried plum improves bone health. These osteoprotective effects are a result, in part, of the antiresorptive properties of the fruit, which appear to be mediated by its polyphenolic compounds. Objective: This study was designed to determine if certain fractions of the polyphenolic compounds in dried plums are responsible for the antiresorptive effects and whether they alter mitogen-activated protein kinase (MAPK) and calcium signaling, which are essential to osteoclast differentiation and activity, under normal and inflammatory conditions. Methods: Six polyphenolic fractions were derived from the total polyphenolic extract of dried plum based on solubility. Initial screening, with the use of the Raw 264.7 monocyte and macrophage cell line, showed that 3 fractions had the most marked capacity to downregulate osteoclast differentiation. This response was confirmed in 2 of the fractions by using primary bone marrow-derived cultures and in all subsequent experiments to determine how osteoclast differentiation and function were altered with a focus on these 2 fractions in primary cultures. Data were analyzed by using ANOVA followed by post hoc analyses. Results: Both of the polyphenol fractions decreased osteoclast differentiation and activity coincident with downregulating nuclear factor of activated T cells, cytoplasmic, calcineurindependent 1 (Nfatc1), which is required for osteoclast differentiation. Calcium signaling, essential for the auto-amplification of Nfatc1, was suppressed by the polyphenolic fractions under normal conditions as indicated by suppressed mRNA expression of costimulatory receptors osteoclastassociated receptor (Oscar), signaling regulatory protein β1 (Sirpb1), and triggering receptor expressed on myeloid cells 2 (Trem2). In contrast, in the presence of tumor necrosis factor α (TNF-α), only Sirpb1 was downregulated. In addition to calcium signaling, phosphorylation of extracellular signal-regulated kinase (Erk) and p38 MAPK, involved in the expression and activation of Nfatc1, was also suppressed by the polyphenolic fractions. Conclusion: These results show that certain types of polyphenolic compounds from dried plum downregulate calcium and MAPK signaling, resulting in suppression of Nfatc1 expression, which ultimately decreases osteoclast formation and activity.
KW - Calcium signaling
KW - Dried plum
KW - Osteoclasts
KW - Osteoporosis
KW - Polyphenols
UR - http://www.scopus.com/inward/record.url?scp=85042937370&partnerID=8YFLogxK
U2 - 10.3945/cdn.117.000406
DO - 10.3945/cdn.117.000406
M3 - Article
AN - SCOPUS:85042937370
SN - 2475-2991
VL - 1
JO - Current Developments in Nutrition
JF - Current Developments in Nutrition
IS - 10
M1 - e000406
ER -