Abstract
Osteoclasts (OCs), the only cells capable of remodeling bone, can demineralize calcium minerals biologically. Naive OCs have limitations for the removal of ectopic calcification, such as in heterotopic ossification (HO), due to their restricted activity, migration and poor adhesion to sites of ectopic calcification. HO is the formation of pathological mature bone within extraskeletal soft tissues, and there are currently no reliable methods for removing these unexpected calcified plaques. In the present study, we develop a chemical approach to modify OCs with tetracycline (TC) to produce engineered OCs (TC-OCs) with an enhanced capacity for targeting and adhering to ectopic calcified tissue due to a broad affinity for calcium minerals. Unlike naive OCs, TC-OCs are able to effectively remove HO both in vitro and in vivo. This achievement indicates that HO can be reversed using modified OCs and holds promise for engineering cells as “living treatment agents” for cell therapy.
Highlights
Osteoclasts (OCs), the only cells capable of remodeling bone, can demineralize calcium minerals biologically
OCs were induced by bone marrow-derived monocyte–macrophage precursor cells (BMMs) stimulated by receptor activator of nuclear factor-κB ligand (RANKL, 50 μg/l) and macrophage colony-stimulating factor (M-CSF, 25 μg/l);[38] OCs obtained in vitro were characterized by tartrate-resistant acid phosphatase (TRAP) staining (Fig. 1b), and their decalcification capacity (Supplementary Fig. 1) and bone-targeting ability were confirmed
Their adhesion ability within ectopic calcified tissue and soft tissues was poor (Supplementary Fig. 2), which was confirmed by previous study[5,6]
Summary
Osteoclasts (OCs), the only cells capable of remodeling bone, can demineralize calcium minerals biologically. We develop a chemical approach to modify OCs with tetracycline (TC) to produce engineered OCs (TC-OCs) with an enhanced capacity for targeting and adhering to ectopic calcified tissue due to a broad affinity for calcium minerals. In vitro and in vivo experiments demonstrate that such engineered OCs are more effective than the native ones in resorbing ectopic calcifications and can be developed as therapeutic cells to remove different types of HO. This achievement shows promise for the use of chemical cells as “living treatment materials” or even “living agents” for biomedical applications
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