Suppression of zinc finger protein 467 alleviates osteoporosis through promoting differentiation of adipose derived stem cells to osteoblasts

Adult bone mass is maintained by an exquisite balance between bone formation by osteoblasts and bone resorption by osteoclasts [1]. Disruption of this delicate equilibrium can lead to osteoporosis (OP), a multifactorial, age-related metabolic bone disease characterized by reduction in bone mass, bone tissue microarchitectural deterioration, and increased fracture risk [2,3].A variety of risk factors have been associated with osteoporosis, with emerging evidence suggesting a close association between bone aging, disease, and stem/progenitor cell defects [4,5]. Numerous animal and human studies have examined the links between mesenchymal or osteoprogenitor cell properties, aging, and osteopenia; however, many results to date have been contradictory and confusing.Interpreting the results of these studies is further complicated by variations in the cell source site, isolation procedures, culture conditions, assay conditions, metrics, and developmental time-points being evaluated. The clearest trends are observed in murine osteoporosis/osteopenia models, including SAMP6 [6,7] and aged C57BL/6 [8] mice, which exhibit low bone mass and/or bone material and mechanical defects accompanied by altered mesenchymal progenitor properties (i.e., reduced numbers, proliferative capacity, or osteogenic differentiation capacity).There are emerging evidences linking osteoporosis and stem cell defects, including osteoblast-progenitors (mesenchymal stem cells, MSCs) residing in the bone marrow [9], so it has been hypothesized that such cells from in vitro culture might be infused back to osteopenic subjects in order to replenish their stem cell pool, which would result in a positive bone balance and ultimately the regeneration of the osteopenic skeleton.Mesenchymal stem cells, the precursor cells of adipocytes and osteoblasts [10], are found to play an important role in bone physiology and partly participate in the pathophysiology of osteoporosis. Indeed, in postmenopausal women who suff