Low-density Lipoprotein Receptor Deficiency Causes Impaired Osteoclastogenesis and Increased Bone Mass in Mice because of Defect in Osteoclastic Cell-Cell Fusion

Multifarious effects of 17-β-estradiol on apolipoprotein E receptors gene expression during osteoblast differentiation <i>in vitro </i>

“…No reports about LDLR affects on osteoblast physiology exist so far. However, Okayasu M et al found impaired osteoclastogenesis and increased bone mass in Ldlr -/-mice because of a defect in osteoclastic cell-cell fusion, and this change was accompanied by decreases in bone resorption parameters, with no changes in bone formation parameters (65). As a receptor for removal of apoE-rich chylomicron remnants, LRP1 plays a predominant role among the LDLR family members in vitamin K1 uptake through chylomicron remnants endocytosis in human osteoblasts (64).…”

Low-density lipoprotein receptor deficiency impaired mice osteoblastogenesis <i>in vitro </i>

“…These authors attributed the reduction in osteoclast formation to a defect in cell-cell fusion of preosteoclasts. Furthermore, these authors demonstrated that the LDLR -/-derived preosteoclasts contained less osteoclast fusion regulator molecules such as Atp6v0d2 and DC-STAMP in the plasma membrane than those from wild-type preosteoclasts (39). However, Chen and colleagues detected decreased bone mass in the LDLR -/-mice, which was associated with decreased Runx2 and Collangen-1 expression during osteoblastogenesis and increased TRAP levels during osteoclastogenesis from bone marrow cells in vitro, implying that the decreased bone mass in LDLR -/-mice was associated with decreased osteoblastic function and increased osteoclastic function in these mice (40).…”

“…In an animal experiment, LDLR deficiency caused ectopic bone formation in an experimental osteoarthritis mouse model (38). Furthermore, Okayasu et al showed that LDLR deficiency induced impaired pre-osteoclast fusion in vitro while increasing bone mass in LDLR deficient mice (39). However, decreased bone mass was detected in LDLR deficient mice with inhibition of osteoblastogenesis from bone marrow cells and enhanced osteoclastogenesis in vitro (40), indicating that LDLR might regulate bone metabolism in a complex manner.…”

Osteocytes Produce Interferon-β as a Negative Regulator of Osteoclastogenesis

“…Western Blot Analysis-After cultivation, cells were washed with PBS and lysed in cell lysis buffer (10 mM sodium phosphate (pH 7.5), 150 mM NaCl, 1.0% Nonidet P-40, 0.5% sodium deoxycholate, 0.1% sodium dodecyl sulfate, 1.0 mM EDTA, 1.0 mM p-aminoethyl-benzenesulfonyl fluoride, 10 g/ml leupeptin, 10 g/ml pepstatin, and 10 g/ml aprotinin), and Western blot analysis was performed as described previously (28).…”