Shuanhu Zhou, PhD, of the Department of Orthopedic Surgery, has found that there are paracrine (cell to cell signaling) effects of blood-forming hematopoietic cells on human mesenchymal stem cells—bone-forming precursors found in bone marrow. His findings appear in Scientific Reports.
With age comes a decline in stem cell function and an increased risk for osteoporosis, bone fractures and skeletal tissue degradation. According to Zhou, what he’s discovered may help identify interventions and therapies to prevent some of these age-related skeletal side effects.
The processes that govern both blood and bone formation are found within the bone marrow of our bodies. Zhou has found that factors secreted by hematopoietic cells (blood forming cells) may stimulate proliferation, contribute to osteoblast differentiation and inhibit senescence of bone-forming cells. Zhou reports that these soluble factors, including TNF-α , PDGF-β , Wnt1, 4, 6, 7a and 10a, sFRP-3 or sFRP-5 may allow hematopoietic cells to interact with mesenchymal stem cells (bone forming precursor cells). In particular, Zhou has found that the secreted factor TNF-α (Tumor Necrosis Factor-α), a multifunctional protein that increases with age, inhibits proliferation and differentiation of osteoblasts.
The new study may point the way toward interventions to prevent osteoporosis and promote skeletal health. Future therapeutic strategies could target the interplay between hematopoietic cells and mesenchymal stem cells, potentially restoring skeletal tissue.
“This report identifies the ways in which marrow hematopoietic cells influence osteoblast differentiation and identifies new targets for optimizing skeletal health,” said Julie Glowacki, PhD, senior scientist and director of the Skeletal Biology Program in the Department of Orthopedic Surgery.
This work was supported by grants from the Gillian Reny Stepping Strong Fund, Department of Orthopedic Surgery, BRI Fund to Sustain Research Excellence and American Federation for Aging Research. Zhou is an associate scientist at BWH, assistant professor of Orthopedic Surgery at Harvard Medical School and affiliated faculty at the Harvard Stem Cell Institute.