Adult Prg4+ progenitors repair long-term articular cartilage wounds in vivo.

The identity and origin of the stem/progenitor cells for adult joint cartilage repair remain unknown, impeding therapeutic development. Simulating the common therapeutic modality for cartilage repair in humans, i.e.

Sclerostin Antibody Administration Increases the Numbers of Sox9creER+ Skeletal Precursors and Their Progeny.

Blocking the Wnt inhibitor, sclerostin, increases the rate of bone formation in rodents and in humans. On a cellular level, the antibody against sclerostin acts by increasing osteoblast numbers partly by activating the quiescent bone-lining cells in vivo. No evidence currently exists, to determine whether blocking sclerostin affects early cells of the osteoblast lineage.

Stem and progenitor cells in skeletal development.

Accumulating evidence supports the idea that stem and progenitor cells play important roles in skeletal development. Over the last decade, the definition of skeletal stem and progenitor cells has evolved from cells simply defined by their in vitro behaviors to cells fully defined by a combination of sophisticated approaches, including serial transplantation assays and in vivo lineage-tracing experiments. These approaches have led to better identification of the characteristics of skeletal stem cells residing in multiple sites, including the perichondrium of the fetal bone, the resting zone of the postnatal growth plate, the bone marrow space and the periosteum in adulthood.

Withdrawal of parathyroid hormone after prolonged administration leads to adipogenic differentiation of mesenchymal precursors in vivo.

Intermittent PTH-like drugs are the only approved so-called anabolic agent that increases bone mass in both mice and humans. It is well documented that PTH targets mature cells of the osteoblast lineage, with only indirect evidence of its actions on early cells of the osteoblast lineage. Using a triple transgenic mouse model that allowed labeling of very early cells of the osteoblast lineage, we traced the progeny of these into osteoblast lineage in adult mice.

Parathyroid hormone regulates fates of murine osteoblast precursors in vivo.

Teriparatide, a recombinant form of parathyroid hormone (PTH), is the only approved treatment for osteoporosis that increases the rate of bone formation. Teriparatide increases osteoblast numbers by suppressing osteoblast apoptosis and activating bone-lining cells. No direct evidence for teriparatide's actions on early cells of the osteoblast lineage has been demonstrated.

Bone CLARITY: Clearing, imaging, and computational analysis of osteoprogenitors within intact bone marrow.

Bone tissue harbors unique and essential physiological processes, such as hematopoiesis, bone growth, and bone remodeling. To enable visualization of these processes at the cellular level in an intact environment, we developed "Bone CLARITY," a bone tissue clearing method. We used Bone CLARITY and a custom-built light-sheet fluorescence microscope to detect the endogenous fluorescence of Sox9-tdTomato osteoprogenitor cells in the tibia, femur, and vertebral column of adult transgenic mice.

Granulocyte-macrophage colony-stimulating factor-dependent CD11c-positive cells differentiate into active osteoclasts.

Levels of circulating cytokines are elevated in inflammatory diseases. Previously, it was shown that interleukin (IL-)17A, in synergism with 1,25-dihydroxyvitamin D [1,25(OH)D] and tumor necrosis factor α (TNFα), induces the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) by murine osteoblasts in vitro. In this study, we further analyzed the effects of GM-CSF on osteoclast development in vitro.

Sclerostin Antibody Administration Converts Bone Lining Cells Into Active Osteoblasts.

Sclerostin antibody (Scl-Ab) increases osteoblast activity, in part through increasing modeling-based bone formation on previously quiescent surfaces. Histomorphometric studies have suggested that this might occur through conversion of bone lining cells into active osteoblasts. However, direct data demonstrating Scl-Ab-induced conversion of lining cells into active osteoblasts are lacking.

Regulation of peripheral classical and non-classical monocytes on infliximab treatment in patients with rheumatoid arthritis and ankylosing spondylitis.

Objective: To investigate the regulatory effect of tumour necrosis factor (TNF) blockade with infliximab on the distribution of peripheral blood monocyte subpopulations in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS).

Methods: Purified CD11b+CD14+ monocytes from 5 patients with RA and 5 AS were analysed ex vivo before and after infliximab treatment by flow cytometry for CD16, CD163, CD11b, C-C chemokine receptor type 2 (CCR2) and CXC chemokine receptor 4 (CXCR4) at baseline and at days 2, 14, 84 and 168 after the first infliximab administration. Serum levels of the stromal cell-derived factor (SDF)-1 and monocyte chemotactic peptide (MCP)-1 at different time points were measured in either patient group before and on infliximab treatment.

Interleukin-17A stimulates granulocyte-macrophage colony-stimulating factor release by murine osteoblasts in the presence of 1,25-dihydroxyvitamin D(3) and inhibits murine osteoclast development in vitro.

Objective: To investigate the effects of interleukin-17A (IL-17A) on osteoclastogenesis in vitro.

Methods: Bone marrow cells (BMCs) were isolated from the excised tibia and femora of wild-type C57BL/6J mice, and osteoblasts were obtained by sequential digestion of the calvariae of ddY, C57BL/6J, and granulocyte-macrophage colony-stimulating factor-knockout (GM-CSF(-/-)) mice. Monocultures of BMCs or cocultures of BMCs and osteoblasts were supplemented with or without 1,25-dihydroxyvitamin D(3)(1,25[OH](2)D(3)), recombinant human macrophage colony-stimulating factor (M-CSF), RANKL, and IL-17A.

Delayed osteoblast differentiation and altered inflammatory response around implants placed in incisor sockets of type 2 diabetic rats.

Objective: Central to the process of osseointegration is the recruitment of mesenchymal progenitor cells to the healing site, their proliferation and differentiation to bone synthesising osteoblasts. The process is under the control of pro-inflammatory cytokines and growth factors. The aim of this study was to monitor these key stages of osseointegration and the signalling milieu during bone healing around implants placed in healthy and diabetic bone.