Glycinol Enhances Osteogenic Differentiation and Attenuates the Effects of Aging on Bone Marrow-derived Mesenchymal Stem Cells

Authors: STRONG, AMY - Tulane University; JONES, ROBERT - Tulane University; GLOWACKI, JULIE - Tulane University; Boue, Stephen; BUROW, MATTHEW - Tulane University; BUNNEL, BRUCE - Tulane University

Submitted to: Journal of Regenerative Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/31/2017
Publication Date: N/A
Citation: N/A

Interpretive Summary: Osteoporosis is characterized by decreased bone mineral density and increased risk of fractures. It is most prevalent in the elderly population, leading to significant morbidity and mortality. Recently, plant estrogens have gained significant attention as an alternative therapy due to their structural similarity to estradiol and their osteogenic (bone-building) potential. One such phytoestrogen is glycinol, which accumulates in soybeans in response to stress or elicitor treatment. In this study, the effects of glycinol were investigated in human bone marrow mesenchymal stem cells derived from young subjects (<25 years old) and old subjects (>55 years old). Stem cells isolated from old subjects demonstrated reduced osteogenic and adipogenic differentiation potential, which correlated with a reduction in the mRNA levels for key osteogenic genes. Stem cells from both young and old subjects exhibited a dose-dependent response to estradiol and glycinol. Exposure to estradiol and glycinol rescued the age-related reduction in osteogenic differentiation of stem cells isolated from old subjects. Additional studies demonstrated enhanced expression of key osteogenic transcription factors following treatment with glycinol, which provides mechanistic support for the increased osteogenesis observed in stem cells following treatment. Together, these studies demonstrate the osteoinductive effects of glycinol on BMSCs and support the further investigation of glycinol as a potential treatment for osteoporosis.

Technical Abstract: Osteoporosis is characterized by decreased bone mineral density and increased risk of fractures. It is most prevalent in the elderly population, leading to significant morbidity and mortality. Recently, phytoestrogens have gained significant attention as an alternative therapy due to their structural similarity to estradiol and their osteogenic potential. One such phytoestrogen is glycinol, which accumulates in soybeans in response to stress or elicitor treatment. In this study, the effects of glycinol were investigated in human bone marrow mesenchymal stem cells (BMSCs) derived from young subjects (<25 years old) and old subjects (>55 years old). BMSCs isolated from young and old subjects were characterized based on differentiation capacity, expression of key osteogenic and adipogenic genes, and expression of estrogen receptors (ER) and downstream estrogen effectors. BMSCs isolated from old subjects demonstrated reduced osteogenic and adipogenic differentiation potential, which correlated with a reduction in the mRNA levels for key osteogenic genes. BMSCs from both young and old subjects exhibited a dose-dependent response to estradiol and glycinol. Exposure to estradiol and glycinol rescued the age-related reduction in osteogenic differentiation of BMSCs isolated from old subjects. Additional studies demonstrated enhanced expression of key osteogenic transcription factors (RUNX2, ALP, SPARC, OPN) following treatment with glycinol, which provides mechanistic support for the increased osteogenesis observed in BMSCs following treatment. Furthermore, glycinol induced the expression of ERa, and ER antagonist studies further support that glycinol promotes osteogenesis through ER signaling. Together, these studies demonstrate the osteoinductive effects of glycinol on BMSCs and support the further investigation of glycinol as a potential treatment for osteoporosis.