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CXCL12 is abundantly expressed in reticular cells associated with the perivascular niches of the bone marrow (BM) and is indispensable for B-lymphopoiesis. Cxcl12 promotes osteoclastogenesis and has been implicated in pathologic bone resorption. We had shown earlier that estrogen receptor α deletion in osteoprogenitors and estrogen deficiency in mice increase Cxcl12 mRNA and protein levels in the BM plasma, respectively. We have now generated female and male mice with conditional deletion of a Cxcl12 allele in Prrx1 targeted cells (Cxcl12 ) and show herein that they have a 90% decrease in B lymphocytes, but increased erythrocytes and adipocytes in the marrow. Ovariectomy increased the expression of Cxcl12 and B cell number in the Cxcl12 control mice, but these effects were abrogated in the Cxcl12 mice. Cortical bone mass was not affected in Cxcl12 mice. Albeit, the cortical bone loss caused by ovariectomy was greatly attenuated. Most unexpectedly, the rate of bone turnover in sex steroid sufficient female or male Cxcl12 mice was dramatically increased, as evidenced by a more than two-fold increase in several osteoblast- and osteoclast- specific mRNAs, as well as increased mineral apposition and bone formation rate and increased osteoclast number in the endosteal surface. The magnitude of the Cxcl12 induced changes were much greater than those caused by ovariectomy or orchidectomy in the Cxcl12 mice. These results strengthen the evidence that CXCL12 contributes to the loss of cortical bone mass caused by estrogen deficiency. Moreover, they reveal for the first time that in addition to its effects on hematopoiesis, CXCL12 restrains bone turnover - without changing the balance between resorption and formation - by suppressing osteoblastogenesis and the osteoclastogenesis support provided by cells of the osteoblast lineage. This article is protected by copyright. All rights reserved.
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Bone-marrow-derived, non-hematopoietic cells that support HEMATOPOETIC STEM CELLS. They have also been isolated from other organs and tissues such as UMBILICAL CORD BLOOD, umbilical vein subendothelium, and WHARTON JELLY. These cells are considered to be a source of multipotent stem cells because they include subpopulations of mesenchymal stem cells.
Cells that can develop into distinct mesenchymal tissue such as BONE; TENDONS; MUSCLES; ADIPOSE TISSUE; CARTILAGE; NERVE TISSUE; and BLOOD and BLOOD VESSELS.
A type of osseous tissue which makes up the inner part of bone. It has a spongy, honeycomb-like structure with struts or trabecula and contains the BONE MARROW. It has higher rate of BONE REMODELING turnover than CORTICAL BONE.
A CXC chemokine that is chemotactic for T-LYMPHOCYTES and MONOCYTES. It has specificity for CXCR4 RECEPTORS. Two isoforms of CXCL12 are produced by alternative mRNA splicing.
A diphosphonate which affects calcium metabolism. It inhibits ectopic calcification and slows down bone resorption and bone turnover.
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