scholarly journals Bone Lining Cells Could Be Sources of Bone Marrow Adipocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Ji Yeon Lee ◽  
Jae-Yeon Yang ◽  
Sang Wan Kim
Keyword(s):  
Bone Marrow ◽  
Immunohistochemical Staining ◽  
Lineage Tracing ◽  
Type I ◽  
Micro Computed Tomography ◽  
Endosteal Surface ◽  
Type I Procollagen ◽  
Bone Marrow Adipocytes ◽  
Osteoblast Lineage ◽  
Pharmacologic Inhibition

BackgroundRecently, lineage-tracing studies demonstrated that parathyroid hormone and anti-sclerostin antibody (Scl-Ab) can convert bone lining cells (BLCs) into active osteoblasts. However, BLCs might also be differentiated into other lineages. Here we investigated whether BLCs could differentiate into bone marrow adipocytes (BMAds) and whether Scl-Ab could suppress this process.MethodsDmp1-CreERt2:mTmG mice were injected with 0.5 mg of 4-hydroxytamoxifen once weekly from postnatal week 4 to week 8. The mice were treated with either vehicle or rosiglitazone for 8 weeks (weeks 12–20). Moreover, they were administered either vehicle or Scl-Ab (50 mg/kg) twice weekly for 4 weeks (weeks 16–20, N = 4–6/group). We chased the GFP+ cells from the endosteal surface to the bone marrow (BM) of the femur. Using immunohistochemical staining, the numbers of perilipin+ or GFP+/perilipin double+ cells in the BM were quantified. In addition, serum N-terminal propeptide of type I procollagen (P1NP) levels were measured at each time point, and bone mass was analyzed at 20 weeks using micro-computed tomography.ResultsScl-Ab administration significantly reversed the decreases in bone parameters induced by rosiglitazone. Plump GFP+ cells, presumably active osteoblasts, and extremely flat GFP+ cells, presumably BLCs, were present on the endosteal surface of the femur at 8 and 12 weeks, respectively, in line with prior findings. When we chased the GFP+ cells, rosiglitazone significantly increased the number of GFP/perilipin double+ BMAds compared to the effects of the vehicle (P < 0.001), and overlapping Scl-Ab administration decreased the number of GFP/perilipin double + BMAd compared to rosiglitazone alone (P < 0.001). In addition, we found that osteoblast lineage cells such as BLCs might express PPARγ on immunohistochemical staining. When rosiglitazone was administered to Rip-Cre:mTmG mice, GFP+ cells were not present on the endosteal surface or in the BM of the femur; however, they were present in the pancreas.ConclusionBLCs could be sources of BMAds, and rosiglitazone could stimulate the differentiation of osteoblast lineage cells into BMAds. Suppression of the differentiation of osteoblast lineage cells into BMAds might contribute to anabolic effects resulting from the pharmacologic inhibition of sclerostin.

scholarly journals Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver

2010 ◽  
Vol 108 (1) ◽  
pp. 308-313 ◽  
Author(s):  
Christoph H. Österreicher ◽  
Melitta Penz-Österreicher ◽  
Sergei I. Grivennikov ◽  
Monica Guma ◽  
Ekaterina K. Koltsova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Liver Disease ◽  
Liver Injury ◽  
Specific Protein ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Type I ◽  
Mesenchymal Transition ◽  
Specific Subset ◽  
Experimental Liver

Cirrhosis is the end result of chronic liver disease. Hepatic stellate cells (HSC) are believed to be the major source of collagen-producing myofibroblasts in cirrhotic livers. Portal fibroblasts, bone marrow-derived cells, and epithelial to mesenchymal transition (EMT) might also contribute to the myofibroblast population in damaged livers. Fibroblast-specific protein 1 (FSP1, also called S100A4) is considered a marker of fibroblasts in different organs undergoing tissue remodeling and is used to identify fibroblasts derived from EMT in several organs including the liver. The aim of this study was to characterize FSP1-positive cells in human and experimental liver disease. FSP1-positive cells were increased in human and mouse experimental liver injury including liver cancer. However, FSP1 was not expressed by HSC or type I collagen-producing fibroblasts. Likewise, FSP1-positive cells did not express classical myofibroblast markers, including αSMA and desmin, and were not myofibroblast precursors in injured livers as evaluated by genetic lineage tracing experiments. Surprisingly, FSP1-positive cells expressed F4/80 and other markers of the myeloid-monocytic lineage as evaluated by double immunofluorescence staining, cell fate tracking, flow cytometry, and transcriptional profiling. Similar results were obtained for bone marrow-derived and peritoneal macrophages. FSP1-positive cells were characterized by increased expression of COX2, osteopontin, inflammatory cytokines, and chemokines but reduced expression of MMP3 and TIMP3 compared with Kupffer cells/macrophages. These findings suggest that FSP1 is a marker of a specific subset of inflammatory macrophages in liver injury, fibrosis, and cancer.

scholarly journals Inhibition of Hif1α prevents both trauma-induced and genetic heterotopic ossification

2015 ◽  
Vol 113 (3) ◽  
pp. E338-E347 ◽  
Author(s):  
Shailesh Agarwal ◽  
Shawn Loder ◽  
Cameron Brownley ◽  
David Cholok ◽  
Laura Mangiavini ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Bone Formation ◽  
Heterotopic Ossification ◽  
De Novo ◽  
Hypoxia Inducible Factor ◽  
Lineage Tracing ◽  
Mechanical Trauma ◽  
Adaptation To Hypoxia ◽  
Type I ◽  
Pharmacologic Inhibition

Pathologic extraskeletal bone formation, or heterotopic ossification (HO), occurs following mechanical trauma, burns, orthopedic operations, and in patients with hyperactivating mutations of the type I bone morphogenetic protein receptor ACVR1 (Activin type 1 receptor). Extraskeletal bone forms through an endochondral process with a cartilage intermediary prompting the hypothesis that hypoxic signaling present during cartilage formation drives HO development and that HO precursor cells derive from a mesenchymal lineage as defined by Paired related homeobox 1 (Prx). Here we demonstrate that Hypoxia inducible factor-1α (Hif1α), a key mediator of cellular adaptation to hypoxia, is highly expressed and active in three separate mouse models: trauma-induced, genetic, and a hybrid model of genetic and trauma-induced HO. In each of these models, Hif1α expression coincides with the expression of master transcription factor of cartilage, Sox9 [(sex determining region Y)-box 9]. Pharmacologic inhibition of Hif1α using PX-478 or rapamycin significantly decreased or inhibited extraskeletal bone formation. Importantly, de novo soft-tissue HO was eliminated or significantly diminished in treated mice. Lineage-tracing mice demonstrate that cells forming HO belong to the Prx lineage. Burn/tenotomy performed in lineage-specific Hif1α knockout mice (Prx-Cre/Hif1αfl:fl) resulted in substantially decreased HO, and again lack of de novo soft-tissue HO. Genetic loss of Hif1α in mesenchymal cells marked by Prx-cre prevents the formation of the mesenchymal condensations as shown by routine histology and immunostaining for Sox9 and PDGFRα. Pharmacologic inhibition of Hif1α had a similar effect on mesenchymal condensation development. Our findings indicate that Hif1α represents a promising target to prevent and treat pathologic extraskeletal bone.

scholarly journals Characterization of rabbit stromal fibroblasts derived from red and yellow bone marrow.

1986 ◽  
Vol 163 (2) ◽  
pp. 400-413 ◽  
Author(s):  
D F Bainton ◽  
M A Maloney ◽  
H M Patt ◽  
R Stern
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Stromal Fibroblasts ◽  
Type I Procollagen ◽  
Yellow Marrow ◽  
Major Species ◽  
Prominent Peak

Rabbit stromal fibroblasts subcultured from red and yellow bone marrow and implanted beneath the renal capsule form ossicles the hemic cellularity of which mirrors the cellularity of the marrow used for culture. Although the cultured red and yellow marrow cells are similar in fine-structural appearance, they differ strikingly in enzymatic content of alpha-naphthylbutyrate esterase, which is abundant only in the cells derived from yellow marrow. Other observers (20, 21) have proposed that stromal fibroblasts are preadipocytes, and this data suggests that those derived from yellow marrow have the phenotype of more differentiated adipocytes. On the other hand, fibroblasts derived from red and yellow bone marrow show no differences in their profiles of procollagen synthesis. Both types of fibroblasts secrete type III procollagen as the major species, with a I/III ratio of 1:3; in contrast, rabbit dermal fibroblasts have a prominent peak of type I procollagen. The similarity of stromal cells derived from red and yellow bone marrow in procollagen synthesis suggests that the collagen part of the extracellular matrix is not the only basis for their intrinsic difference in capacity for hematopoiesis.

Hematopoiesis is severely altered in mice with an induced osteoblast deficiency

Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3258-3264 ◽  
Author(s):  
Dora Visnjic ◽  
Zana Kalajzic ◽  
David W. Rowe ◽  
Vedran Katavic ◽  
Joseph Lorenzo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transgenic Animals ◽  
Extramedullary Hematopoiesis ◽  
Type I ◽  
Specific Expression ◽  
Hematopoietic Stem ◽  
Marrow Cellularity ◽  
Osteoblast Lineage

Abstract We previously reported a transgenic mouse model expressing herpesvirus thymidine kinase (TK) gene under the control of a 2.3-kilobase fragment of the rat collagen α1 type I promoter (Col2.3ΔTK). This construct confers lineage-specific expression in developing osteoblasts, allowing the conditional ablation of osteoblast lineage after treatment with ganciclovir (GCV). After GCV treatment these mice have profound alterations on bone formation leading to a progressive bone loss. In addition, treated animals also lose bone marrow cellularity. In this report we characterized hematopoietic parameters in GCV-treated Col2.3ΔTK mice, and we show that after treatment transgenic animals lose lymphoid, erythroid, and myeloid progenitors in the bone marrow, followed by decreases in the number of hematopoietic stem cells (HSCs). Together with the decrease in bone marrow hematopoiesis, active extramedullary hematopoiesis was observed in the spleen and liver, as measured by an increase in peripheral HSCs and active primary in vitro hematopoiesis. After withdrawal of GCV, osteoblasts reappeared in the bone compartment together with a recovery of medullary and decrease in extramedullary hematopoiesis. These observations directly demonstrate the role of osteoblasts in hematopoiesis and provide a model to study the interactions between the mesenchymal and hematopoietic compartments in the marrow. (Blood. 2004; 103:3258-3264)

scholarly journals Topical co‐administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hideki Ueyama ◽  
Yoichi Ohta ◽  
Yuuki Imai ◽  
Akinobu Suzuki ◽  
Ryo Sugama ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Structure ◽  
Precursor Cells ◽  
The Other ◽  
Bone Morphogenetic Protein 2 ◽  
New Bone Formation ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Left Femur

Abstract Background Bone morphogenetic proteins (BMPs) induce osteogenesis in various environments. However, when BMPs are used alone in the bone marrow environment, the maintenance of new bone formation is difficult owing to vigorous bone resorption. This is because BMPs stimulate the differentiation of not only osteoblast precursor cells but also osteoclast precursor cells. The present study aimed to induce and maintain new bone formation using the topical co-administration of recombinant human BMP-2 (rh-BMP-2) and zoledronate (ZOL) on beta-tricalcium phosphate (β-TCP) composite. Methods β-TCP columns were impregnated with both rh-BMP-2 (30 µg) and ZOL (5 µg), rh-BMP-2 alone, or ZOL alone, and implanted into the left femur canal of New Zealand white rabbits (n = 56). The implanted β-TCP columns were harvested and evaluated at 3 and 6 weeks after implantation. These harvested β-TCP columns were evaluated radiologically using plane radiograph, and histologically using haematoxylin/eosin (H&E) and Masson’s trichrome (MT) staining. In addition, micro-computed tomography (CT) was performed for qualitative analysis of bone formation in each group (n = 7). Results Tissue sections stained with H&E and MT dyes revealed that new bone formation inside the β-TCP composite was significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Micro-CT data also demonstrated that the bone volume and the bone mineral density inside the β-TCP columns were significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Conclusions The topical co-administration of both rh-BMP-2 and ZOL on β-TCP composite promoted and maintained newly formed bone structure in the bone marrow environment.

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