Pax5-deficient mice exhibit early onset osteopenia with increased osteoclast progenitors.
Pax5 encodes BSAP, a member of the paired box domain transcription factors, whose expression is restricted to B lymphocyte lineage cells. Pax5(-/-) mice have a developmental arrest of the B cell lineage at the pro-B cell stage. We show here that Pax5(-/-) mice are severely osteopenic, missing 60% of their bone mass. The osteopenia can be accounted for by a >100% increase in the number of osteoclasts in bone measured histomorphometrically. This is not due to a lack of B cells, because other strains of B cell-deficient mice do not exhibit this phenotype. There was no difference in the number of osteoclasts produced in vitro by wild-type and Pax5(-/-) bone marrow cells. In contrast, spleen cells from Pax5(-/-) mice produce as much as five times the number of osteoclasts as control spleen cells. Culture of Pax5(-/-) spleen cells yields a population of adherent cells that grow spontaneously in culture without added growth factors for >4 wk. These cells have a monocyte phenotype, produce large numbers of osteoclasts when induced in vitro, and therefore are highly enriched in osteoclast precursors. These data demonstrate a previously unsuspected connection between B cell and osteoclast development and a key role for Pax5 in the control of osteoclast development.
Horowitz
Mark C
MC
Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT 06510, USA. mark.horowitz@yale.edu
Xi
Yougen
Y
Pflugh
David L
DL
Hesslein
David G T
DG
Schatz
David G
DG
Lorenzo
Joseph A
JA
Bothwell
Alfred L M
AL
D000818:Animals; D001851:Bone Diseases, Metabolic / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D006130:Growth Disorders / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016130:Immunophenotyping; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology*; D051757:PAX5 Transcription Factor; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*
D004268:DNA-Binding Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D014157:Transcription Factors