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^∆Prrx1) 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^f/f control mice, but these effects were abrogated in the Cxcl12^∆Prrx1 mice. Cortical bone mass was not affected in Cxcl12^∆Prrx1 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^∆Prrx1 mice was dramatically increased, as evidenced by a more than twofold 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^∆Prrx1‐induced changes were much greater than those caused by ovariectomy or orchidectomy in the Cxcl12^f/f 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. © 2020 American Society for Bone and Mineral Research.

中文翻译：

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间充质细胞中的 Cxcl12 缺失增加了骨周转率并减轻了小鼠雌激素缺乏引起的皮质骨损失。

CXCL12 在与骨髓 (BM) 的血管周围壁龛相关的网状细胞中大量表达，并且对于 B 淋巴细胞生成是必不可少的。Cxcl12促进破骨细胞生成并与病理性骨吸收有关。我们之前已经表明，骨祖细胞中的雌激素受体 α 缺失和小鼠中的雌激素缺乏分别增加了 BM 血浆中的Cxcl12 mRNA 和蛋白质水平。我们现在已经生成了在 Prrx1 靶向细胞（Cxcl12 ^{ΔPrrx1 ）中条件性缺失}Cxcl12等位基因的雌性和雄性小鼠，并在本文中表明它们的 B 淋巴细胞减少了 90%，但骨髓中的红细胞和脂肪细胞增加。卵巢切除术增加了表达Cxcl12 ^{f/f对照小鼠中的}Cxcl12和 B 细胞数量，但这些影响在Cxcl12 ^ΔPrrx1小鼠中被消除。Cxcl12 ^ΔPrrx1小鼠的皮质骨量不受影响。尽管如此，卵巢切除术引起的皮质骨丢失已大大减轻。最出人意料的是，性类固醇充足的雌性或雄性Cxcl12 ^ΔPrrx1小鼠的骨转换率显着增加，这可以通过几种成骨细胞和破骨细胞特异性 mRNA 增加两倍以上以及矿物质沉积和骨骼增加来证明形成率和增加骨内膜表面的破骨细胞数量。Cxcl12 ^ΔPrrx1的幅度在Cxcl12 ^f/f小鼠中，由卵巢切除术或睾丸切除术引起的变化要大得多。这些结果加强了 CXCL12 有助于由雌激素缺乏引起的皮质骨量损失的证据。此外，他们首次揭示，除了对造血的影响外，CXCL12 通过抑制成骨细胞生成和成骨细胞谱系细胞提供的破骨细胞生成支持来抑制骨转换——而不改变吸收和形成之间的平衡。© 2020 美国骨与矿物研究学会。