Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice

Stromal Cell-Derived Factor-1β Potentiates Bone Morphogenetic Protein-2-Stimulated Osteoinduction of Genetically Engineered Bone Marrow-Derived Mesenchymal Stem CellsIn Vitro

“…[37][38][39] Among osteoinductive growth factors, BMPs are well known to drive bone formation in vitro and in vivo 40 by enhancing the recruitment of osteoblast progenitor cells and angiogenesis as well as promoting the osteogenic differentiation of MSCs. 41,42 We asked whether it was possible for SDF-1b to potentiate BMP-2-regulated osteogenic differentiation. Using our novel Tet-Off-SDF-1b BMSCs, we demonstrated for the first time that SDF-1b significantly accelerated and enhanced calcium mineral deposition compared to controls, independent of BMP-2 costimulation.…”

Circulating osteogenic cells: Implications for injury, repair, and regeneration

“…The frequency of these cells was extremely low in humans, but they were more abundant in experimental animals (e.g., guinea pigs). (22,23) (12,13) In addition to the success of isolating circulating MSCs from peripheral blood of postnatal organisms, circulating MSC-like cells were also isolated from umbilical cord blood. (26,27) Plastic-nonadherent cells Long et al reported that bone marrow plastic-nonadherent cells, isolated by osteocalcin (OCN) or osteopontin antibodies, may represent a more primitive osteoprogenitor cell population based on their clonal growth kinetics.…”

“…(16,62,63) Animal models of ectopic bone formation also support the notion of COP cell involvement in lesion formation. (12,13,16) In a rare genetic disorder of HO, FOP, patients with active episodes of extraskeletal bone formation have higher numbers of clonally derived COP cell colonies than patients with stable disease or unaffected individuals, and these COP cells are present in early fibroproliferative lesions. (16) The process of vascular calcification was formerly considered the result of passive calcium deposition but is now recognized to be an active pathophysiological process resulting in de novo bone formation in the late stages.…”

“…(49) It is also established in a mouse model of BMP-2-induced HO, where osteoprogenitor cells expressing CXCR4 migrate from the bone marrow to regions of ectopic bone formation by SDF-1 chemoattraction. (12,13) BMP may play roles in both bone formation and attraction of inflammatory cells. (84) BMP stimulation of brown adipocytes may also lower tissue oxygen tension, (85) thereby promoting local chondrogenesis and inducing SDF-1.…”

Mesenchymal Stem Cells in Bone Regeneration

“…Additionally, these circulating cells differentiate and become osteoblasts within the ectopic bone. 25 Definitive proof that endogenous MSCs could migrate from the bone marrow to the systemic circulation was provided by Pitchford et al with the injection of a CXCR4 antagonist. 26 In another study, BM-MSC in systemic circulation are able to home to the site of an injury, but do not differentiate into osteoblasts or chondrocytes and contribute to the callus as one might expect given their behavior in vitro.…”