BioScience Trends. 2017;11(6):658-666. (DOI: 10.5582/bst.2017.01267)

Low-density lipoprotein receptor deficiency impaired mice osteoblastogenesis in vitro.

Zhang N, Zhang Y, Lin J, Qiu XM, Chen LT, Pan XY, Lu YH, Zhang JL, Wang Y, Li DJ, Wang L


Postmenopausal osteoporosis affected most elderly women with co-existence of lipid and bone metabolism disorders. However, the cellular and molecular mechanisms underlying the parallel progression and cross-talk of these systems remained unclear. In the present study, low-density lipoprotein receptor knockout (LDLR-/-) mice were chosen to elucidate the effect of LDLR in regulating the differentiation of osteoblasts, which were responsible for bone formation and modulation of osteoclastogenesis. Primary osteoblasts were isolated from the calvarium of newborn LDLR-/- or wild-type mice followed by osteoblastic differentiation culture in vitro. Alkaline phosphatase activity was significantly decreased in LDLR-/- osteoblasts compared to wild-type controls, combined with calcium deposit formation delay, implying impaired osteoblastogenesis in vitro. Consistent with these findings, the expression of runt-related transcription factor 2 (Runx2) was decreased 3 days after differentiation in LDLR-/- osteoblasts compared to wild-type controls. Moreover, the expression of Osterix was decreased 7 days after differentiation in LDLR-/- osteoblasts compared to wild-type controls, later than Runx2. However, the osteoclastogenesis modulation role of osteoblasts was unaffected by the LDLR deficiency, evidenced by the same level of osteoprotegerin (OPG)/receptor activator of nuclear factor-κ B ligand (RANKL) axis between LDLR-/- and wild-type control osteoblasts. Our results provide a novel insight into the role of LDLR during osteoblastic differentiation and improve understanding of cross-talk between bone and lipid metabolisms.

KEYWORDS: Postmenopausal osteoporosis, low-density lipoprotein receptor, osteoblast, osteoblastogenesis, alkaline phosphatase, runt-related transcription factor 2, Osterix

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