Biomaterial Database

Androgens regulate bone marrow B lymphopoiesis in male mice by targeting osteoblast-lineage cells. 2015

Anna S Wilhelmson, and Alexandra Stubelius, and Anna E Börjesson, and Jianyao Wu, and Anna Stern, and Stephen Malin, and Inga-Lill Mårtensson, and Claes Ohlsson, and Hans Carlsten, and Åsa Tivesten

Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., Å.T.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden; Centre for Bone and Arthritis Research (A.Stu., A.E.B., J.W., C.O., H.C.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden; Department of Rheumatology and Inflammation Research (A.Ste., I.-L.M.), University of Gothenburg, 405 30 Gothenburg, Sweden; and Department of Medicine (S.M.), Center for Molecular Medicine, Karolinska Institute, Karolinska University Hospital, 171 76 Stockholm, Sweden.

Testosterone has profound immune-modulatory actions, which may be important for the sexual dimorphism in immune-related disorders, such as autoimmune diseases. A well-known effect of androgens is inhibition of bone marrow B lymphopoiesis; however, a plausible target cell for this effect has not yet been presented. The aim of this study was to determine the target cell for androgen-mediated regulation of bone marrow B lymphopoiesis in males. We confirm higher number of bone marrow B cells in male mice with global inactivation of the androgen receptor (AR) and these global AR knockout (G-ARKO) mice had increased number of B cell precursors from the pro-B stage. Because osteoblast-lineage cells are known to support B lymphopoiesis at the pro-B stage, we investigated the effect on B lymphopoiesis in osteoblast-lineage cell-specific ARKO (O-ARKO) mice; O-ARKO mice had increased number of B cells in the bone marrow, and the number of B cell precursors was increased from the pro-B stage, demonstrating that O-ARKO mimics the bone marrow B lymphopoiesis pattern of G-ARKO mice. By contrast, O-ARKO mice displayed only minor changes in B cell numbers in the splenic compartment compared with G-ARKO. Further, O-ARKO mice had moderately reduced number of bone trabeculae in the vertebrae, whereas cortical bone was unaffected. In conclusion, androgens exert inhibitory effects on bone marrow B lymphopoiesis in males by targeting the AR in osteoblast-lineage cells. The identification of the likely target cell for androgen-mediated regulation of bone marrow B lymphopoiesis will contribute to elucidation of the mechanisms by which androgens modulate immune-related disorders.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010006	Osteoblasts	Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.	Osteoblast
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D011944	Receptors, Androgen	Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA.	Androgen Receptors,5 alpha-Dihydrotestosterone Receptor,Androgen Receptor,Dihydrotestosterone Receptors,Receptor, Testosterone,Receptors, Androgens,Receptors, Dihydrotestosterone,Receptors, Stanolone,Stanolone Receptor,Testosterone Receptor,5 alpha Dihydrotestosterone Receptor,Androgens Receptors,Receptor, 5 alpha-Dihydrotestosterone,Receptor, Androgen,Receptor, Stanolone,Stanolone Receptors,alpha-Dihydrotestosterone Receptor, 5
D001853	Bone Marrow	The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.	Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D000728	Androgens	Compounds that interact with ANDROGEN RECEPTORS in target tissues to bring about the effects similar to those of TESTOSTERONE. Depending on the target tissues, androgenic effects can be on SEX DIFFERENTIATION; male reproductive organs, SPERMATOGENESIS; secondary male SEX CHARACTERISTICS; LIBIDO; development of muscle mass, strength, and power.	Androgen,Androgen Receptor Agonist,Androgen Effect,Androgen Effects,Androgen Receptor Agonists,Androgenic Agents,Androgenic Compounds,Agents, Androgenic,Agonist, Androgen Receptor,Agonists, Androgen Receptor,Compounds, Androgenic,Effect, Androgen,Effects, Androgen,Receptor Agonist, Androgen,Receptor Agonists, Androgen
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001402	B-Lymphocytes	Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.	B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D013154	Spleen	An encapsulated lymphatic organ through which venous blood filters.
D015415	Biomarkers	Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc.	Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune