Musculoskeletal Disease Center, VA Loma Linda Healthcare Systems, Loma Linda, CA 92357, USA.
Departments of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Cells. 2022 Mar 12;11(6):977. doi: 10.3390/cells11060977.
Tetraspanin3 (TSPAN3) was identified as a binding partner of claudin11 (CLDN11) in osteoblasts and other cell types. Mice with targeted disruption of exhibited trabecular bone mass deficit caused by reduced bone formation and osteoblast function. To determine if the disruption of CLDN11 interacting protein gene results in a similar skeletal phenotype as that of knockout (KO) mice, we generated homozygous KO and heterozygous control mice and characterized their skeletal phenotypes at 13 weeks of age. Micro-CT measurements of the secondary spongiosa of the distal femur revealed 17% and 29% reduction in trabecular bone volume adjusted for tissue volume (BV/TV) in the male and female mice, respectively. Similarly, trabecular BV/TV of the proximal tibia was reduced by 19% and 20% in the male and female mice, respectively. The reduced trabecular bone mass was caused primarily by reduced trabecular thickness and number, and increased trabecular spacing. Consistent with the reduced bone formation as confirmed by histomorphometry analyses, serum alkaline phosphatase was reduced by 11% in the KO mice as compared with controls. Our findings indicate that TSPAN3 is an important positive regulator of osteoblast function and trabecular bone mass, and the interaction of TSPAN3 with CLDN11 could contribute in part to the bone forming effects of Cldn11 in mice.
四跨膜蛋白 3（TSPAN3）被鉴定为成骨细胞和其他细胞类型中 Claudin11（CLDN11）的结合伴侣。靶向敲除 的小鼠表现出小梁骨量减少，这是由于骨形成和成骨细胞功能降低所致。为了确定 CLDN11 相互作用蛋白基因 的破坏是否会导致与 敲除（KO）小鼠相似的骨骼表型，我们生成了纯合 KO 和杂合对照小鼠，并在 13 周龄时对其骨骼表型进行了特征描述。对远端股骨次级松质骨的 micro-CT 测量显示，雄性和雌性小鼠的骨小梁体积调整后的组织体积（BV/TV）分别减少了 17%和 29%。同样，雄性和雌性小鼠的近端胫骨的小梁 BV/TV 分别减少了 19%和 20%。小梁骨量减少主要是由于小梁厚度和数量减少，以及小梁间距增加所致。与组织形态计量学分析证实的骨形成减少一致，KO 小鼠的血清碱性磷酸酶比对照组降低了 11%。我们的研究结果表明，TSPAN3 是成骨细胞功能和小梁骨量的重要正调节因子，TSPAN3 与 CLDN11 的相互作用可能部分有助于 Cldn11 在小鼠中的成骨作用。
