Cathepsin S controls adipocytic and osteoblastic differentiation, bone turnover, and bone microarchitecture

Rauner, Martina; Föger-Samwald, Ursula; Kurz, Martina; Brünner-Kubath, C.; Schamall, Doris; Kapfenberger, A.; Варга, П.; Kudlacek, Stefan; Wutzl, Arno; Höger, Harald; Zysset, Philippe; Shi, Guo‐Ping; Hofbauer, Lorenz C.; Sipos, Wolfgang; Pietschmann, Péter

doi:10.1016/j.bone.2014.04.022

Cited by 34 publications

(28 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bone marrow was flushed from the long bones of wild-type C57BL/6 mice cultured as previously described (25). Briefly bone marrow was seeded at a density of 500 000 cells/cm 2 in DMEM containing 10% fetal calf serum and 1% penicillin/streptomycin (all from Invitrogen).…”

Section: Bone Marrow-derived Osteoblast Differentiation and Stimulatimentioning

confidence: 99%

See 1 more Smart Citation

Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1

et al. 2015

View full text Add to dashboard Cite

Thyroid hormones are key regulators of bone homeostasis, and Wnt signaling has been implicated in thyroid hormone-associated bone loss. Here we tested whether hyperthyroidism and hypothyroidism interfere with dickkopf-1 (DKK1) and sclerostin, two inhibitors of Wnt signaling. Twelve-week-old male C57BL/6 mice were rendered either hyperthyroid or hypothyroid. Hyperthyroid mice displayed decreased trabecular (-54%, P < .001) and cortical bone density (-5%, P < .05) and reduced cortical thickness (-15%, P < .001), whereas hypothyroid mice showed a higher trabecular bone density (+26%, P < .001) with unchanged cortical bone parameters. Histomorphometry and biochemical markers of bone remodeling indicated high bone turnover in hyperthyroid mice and low bone turnover in hypothyroid mice. In vivo, serum DKK1 concentrations were decreased in hyperthyroid mice (-24%, P < .001) and increased in hypothyroid mice (+18%, P < .01). The increase of the number of DKK1-positive cells in hypothyroid mice was confirmed at the tissue level. Interestingly, sclerostin was increased in both disease models, although to a higher extent in hyperthyroid mice (+50%, P < .001, and +24%, P < .05). Serum sclerostin concentrations adjusted for bone mass were increased by 3.3-fold in hyperthyroid (P < .001) but not in hypothyroid mice. Consistently, sclerostin mRNA expression and the number of sclerostin-positive cells were increased in hyperthyroid but not in hypothyroid mice. Our data show that thyroid hormone-induced changes in bone remodeling are associated with a divergent regulation of DKK1 and sclerostin. Thus, the modulation of Wnt signaling by thyroid hormones may contribute to thyroid hormone-associated bone disease and altered expression of Wnt inhibitors may emerge as potential therapeutic targets.

show abstract

Section: Bone Marrow-derived Osteoblast Differentiation and Stimulatimentioning

confidence: 99%

“…Dynamic bone histomorphometry was performed as described previously (25). Briefly, two ip injections of the boneseeking fluorescent dye calcein (20 mg/kg; Sigma) were made 10 and 3 days before the animals were killed.…”

Section: Bone Histomorphometrymentioning

confidence: 99%

Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1

et al. 2015

View full text Add to dashboard Cite

show abstract

“…37,38 Cells were maintained in growth medium (DMEM with 10% FCS and 1% penicillin/streptomycin) until 70% confluence before they were switched to differentiation media (growth medium supplemented with 100 mM ascorbate phosphate and 5 mM β-glycerol phosphate, both from Sigma-Aldrich) for up to 21 days. To delete Wnt5a expression in vitro, cells were treated with 1 mM tamoxifen (Sigma-Aldrich) for 3 days prior to starting the differentiation process.…”

Section: Culture Of Murine Bone Marrow Stromal Cellsmentioning

confidence: 99%

Wnt5a is a key target for the pro-osteogenic effects of iron chelation on osteoblast progenitors

et al. 2016

Self Cite

View full text Add to dashboard Cite

“…Murine bone marrow stromal cells were obtained by flushing the bone marrow from femur and tibia with PBS. Cells were maintained in DMEM with 20% FBS and antibiotics until 70% confluence, when they were differentiated into osteoblasts by treatment with 100 μM ascorbate phosphate and 5 mM β-glycerol phosphate for 10 days and medium replacement every 2 days [26]. Other bone marrow cells were differentiated into osteoclasts by their culture in α-MEM (Sigma-Aldrich) supplemented with 10% FBS and antibiotics, 25 ng/ml recombinant macrophage colony stimulating factor and 50 ng/ml RANKL (PreproTech, Rocky Hill, NJ, USA) for 10 days and medium replacement every 2 days [27].…”

Section: Methodsmentioning

confidence: 99%

Prolactin blocks the expression of receptor activator of nuclear factor κB ligand and reduces osteoclastogenesis and bone loss in murine inflammatory arthritis

et al. 2017

View full text Add to dashboard Cite

BackgroundProlactin (PRL) reduces joint inflammation, pannus formation, and bone destruction in rats with polyarticular adjuvant-induced arthritis (AIA). Here, we investigate the mechanism of PRL protection against bone loss in AIA and in monoarticular AIA (MAIA).MethodsJoint inflammation, trabecular bone loss, and osteoclastogenesis were evaluated in rats with AIA treated with PRL (via osmotic minipumps) and in mice with MAIA that were null (Prlr-/-) or not (Prlr+/+) for the PRL receptor. To help define target cells, synovial fibroblasts from Prlr+/+ mice were treated or not with proinflammatory cytokines ((Cyt), including TNFα, IL-1β, and interferon (IFN)γ) with or without PRL, and these synovial cells were co-cultured or not with bone marrow osteoclast progenitors from Prlr+/+ or Prlr-/- mice.ResultsIn AIA, PRL treatment reduced joint swelling, increased trabecular bone area, lowered osteoclast density, and reduced mRNA levels of osteoclast-associated genes (tartrate-resistant acid phosphatase (Trap)), cathepsin K (Ctsk), matrix metalloproteinase 9 (Mmp9), and receptor activator of nuclear factor κB or RANK (Tnfrsf11a)), of genes encoding cytokines with osteoclastogenic activity (Tnfa, Il1b, Il6, and receptor activator of nuclear factor κB ligand or RANKL (Tnfrsf11)), and of genes encoding for transcription factors and cytokines related to T helper (Th)17 cells (Rora, Rorc, Il17a, Il21, Il22) and to regulatory T cells (Foxp3, Ebi3, Il12a, Tgfb1, Il10). Prlr-/- mice with MAIA showed enhanced joint swelling, reduced trabecular bone area, increased osteoclast density, and elevated expression of Tnfa, Il1b, Il6, Trap, Tnfrsf11a, Tnfrsf11, Il17a, Il21, Il22, 1 l23, Foxp3, and Il10. The expression of the long PRL receptor form increased in arthritic joints, and in synovial membranes and cultured synovial fibroblasts treated with Cyt. PRL induced the phosphorylation/activation of signal transducer and activator of transcription-3 (STAT3) and inhibited the Cyt-induced expression of Il1b, Il6, and Tnfrsf11 in synovial fibroblast cultures. The STAT3 inhibitor S31-201 blocked inhibition of Tnfrsf11 by PRL. Finally, PRL acted on both synovial fibroblasts and osteoclast precursor cells to downregulate Cyt-induced osteoclast differentiation.ConclusionPRL protects against osteoclastogenesis and bone loss in inflammatory arthritis by inhibiting cytokine-induced expression of RANKL in joints and synovial fibroblasts via its canonical STAT3 signaling pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1290-4) contains supplementary material, which is available to authorized users.

show abstract

Cathepsin S controls adipocytic and osteoblastic differentiation, bone turnover, and bone microarchitecture

Cited by 34 publications

References 42 publications

Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1

Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1

Wnt5a is a key target for the pro-osteogenic effects of iron chelation on osteoblast progenitors

Prolactin blocks the expression of receptor activator of nuclear factor κB ligand and reduces osteoclastogenesis and bone loss in murine inflammatory arthritis

Contact Info

Product

Resources

About