Protocatechuic Acid Induces Expression of Osteogenic Genes in Human Osteoblast Cultures: Implications for the Treatment of Osteoporosis and Fractures

Author(s): Lanny L. Johnson, Peter Chen, Darryl D’Lima PhD

Background: Osteoporosis, a condition characterized by a pathologic decrease in bone density, is a common disorder in the elderly. Although anti-resorptive agents that target osteoclasts (e.g., bisphosphonates) are available to treat this condition, very few of the current drugs were of anabolic nature and designed to target osteoblasts. Protocatechuic acid (PCA, 3,4-dihydroxybenzoic acid), a nutraceutical is one such reagent.

Purpose: This proof-of-concept study was designed to determine whether PCA, an abundant natural phenolic acid, promotes gene expression in human osteoblasts in culture.

Methods: Osteogenic and anti-osteogenic gene expression was evaluated by quantitative reverse transcription-polymerase chain reaction in osteoblasts cultured for 12 days with increasing concentrations (1 μM – 100 μM) of PCA.

Results: PCA induced osteopontin (SSP1), bone sialoprotein (IBSP), tissue nonspecific alkaline phosphatase (ALPL), and bone morphogenetic protein 6 (BMP6), but not RUNX2 expression over levels detected in untreated osteoblast cultures (negative control). Interestingly, peak SSP1 expression observed in response to the highest PCA concentrations (50 μM – 100 μM) exceeded levels detected in cultures maintained in commercial osteogenic medium (positive control). By contrast, although PCA induced the expression of IL1B, both TNF and MMP1 were downregulated compared to untreated controls.

Conclusion: The results of this study revealed that PCA had a prominent impact on osteogenic and anti-osteogenic gene expression in human osteoblasts. Further research will be needed to determine if PCA or a biochemical derivative might be used clinically as part of an effective regimen to treat osteoporosis, bone metabolism and fractures.