耐酒石酸磷酸酶(TRAP/ACP5)以性别和部位特异性的方式促进小鼠骨长、调节皮质和骨小梁的骨量以及维持生长板的结构和宽度。

IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Bone Pub Date : 2024-08-05 DOI:10.1016/j.bone.2024.117223
Bhavik Rathod , Suchita Desai , Hasmik Jasmine Samvelyan , Laura Bock , Jianyao Wu , Claes Ohlsson , Anders Palmquist , Jessica J. Alm , Phillip T. Newton , Göran Andersson , Sara H. Windahl
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摘要

抗酒石酸磷酸酶(TRAP)血清水平反映了破骨细胞数量、骨重塑活性和骨折风险。TRAP 的缺失或功能丧失会导致小鼠和人类身材矮小。然而,TRAP 对骨骼和软骨的部位和性别特异性发育的影响和机制尚不十分清楚。在这里,我们利用全基因组TRAP基因敲除(TRAPKO)小鼠和野生型同窝对照(WT)小鼠来研究TRAP可能是骨骼和生长板发育的性别和部位特异性调节因子。与WT小鼠相比,TRAPKO小鼠的体重更轻,胫骨长度更短。这些变化与生长的普遍降低无关,因为并非所有器官的质量都按比例降低,而且血清 IGF-1 也没有变化。通过对皮质骨进行μCT和位点特异性分析,发现与WT小鼠相比,雄性TRAPKO小鼠的胫骨近端更宽、骨小梁厚度更高、骨小梁分离度更低,而雌性小鼠则没有这种效应。组织形态学分析表明,TRAPKO 小鼠的生长板高度和末端肥大软骨细胞高度明显增加,而雌雄小鼠的骨柱数量均减少。这些影响在雌性小鼠中更为明显。TRAPKO小鼠的骨髓巨噬细胞增殖和分化为破骨细胞以及C端交叉连接均正常。总之,我们的研究结果表明,TRAP以性别和部位特异性的方式调节小鼠骨骼和软骨的发育。
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Tartrate-resistant acid phosphatase (TRAP/ACP5) promotes bone length, regulates cortical and trabecular bone mass, and maintains growth plate architecture and width in a sex- and site-specific manner in mice

Tartrate-resistant acid phosphatase (TRAP) serum levels reflect osteoclast number, bone remodeling activity, and fracture risk. Deletion or loss of function of TRAP results in short stature in mice and man. Yet, the impact and mechanisms of TRAP for the site- and sex-specific development of bone and cartilage is not well understood. Here, we use a global TRAP knockout (TRAPKO) and wildtype littermate control (WT) mice of both sexes to investigate TRAP as a possible sex- and site-specific regulator of bone and growth plate development. TRAPKO mice of both sexes weighed less and had shorter tibial length than their WT, features that were more accentuated in male than female TRAPKO mice. These changes were not associated with a general reduction in growth as not all organs displayed a proportionally lower mass, and serum IGF-1 was unchanged. Using μCT and site-specificity analysis of the cortical bone revealed wider proximal tibia, a higher trabecular thickness, and lower trabecular separation in male TRAPKO compared to WT mice, an effect not seen in female mice. Histomorphometric analysis revealed that the growth plate height as well as height of terminal hypertrophic chondrocytes were markedly increased, and the number of columns was decreased in TRAPKO mice of both sexes. These effects were more accentuated in female mice. Proliferation and differentiation of bone marrow derived macrophages into osteoclasts, as well as C-terminal cross links were normal in TRAPKO mice of both sexes. Collectively, our results show that TRAP regulates bone and cartilage development in a sex-and site-specific manner in mice.

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来源期刊
Bone
Bone 医学-内分泌学与代谢
CiteScore
8.90
自引率
4.90%
发文量
264
审稿时长
30 days
期刊介绍: BONE is an interdisciplinary forum for the rapid publication of original articles and reviews on basic, translational, and clinical aspects of bone and mineral metabolism. The Journal also encourages submissions related to interactions of bone with other organ systems, including cartilage, endocrine, muscle, fat, neural, vascular, gastrointestinal, hematopoietic, and immune systems. Particular attention is placed on the application of experimental studies to clinical practice.
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