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更新于：2025-05-07

PHOSPHO1

更新于：2025-05-07

基本信息

别名

PHOSPHO1、Phosphoethanolamine/phosphocholine phosphatase、phosphoethanolamine/phosphocholine phosphatase 1

简介

Phosphatase that has a high activity toward phosphoethanolamine (PEA) and phosphocholine (PCho) (PubMed:15175005). Involved in the generation of inorganic phosphate for bone mineralization (By similarity). Acts in a non-redundant manner with PHOSPHO1 in skeletal mineralization: while PHOSPHO1 mediates the initiation of hydroxyapatite crystallization in the matrix vesicles (MVs), ALPL/TNAP catalyzes the spread of hydroxyapatite crystallization in the extracellular matrix (By similarity).

关联

项与 PHOSPHO1 相关的药物

ML-086

靶点

PHOSPHO1

作用机制

PHOSPHO1 inhibitors

在研机构-

原研机构

Sanford Burnham Prebys Medical Discovery Institute

在研适应症-

非在研适应症

心血管疾病

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PHOSPHO1 相关的临床结果

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100 项与 PHOSPHO1 相关的转化医学

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0 项与 PHOSPHO1 相关的专利（医药）

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101

项与 PHOSPHO1 相关的文献（医药）

2025-04-01·Journal of Oral Biosciences

Histochemical assessment of the anabolic effects of abaloparatide on the femoral metaphyses of ovariectomized mice

Article

作者: Liu, Xuanyu ; Amizuka, Norio ; Cui, Jiaxin ; Sakakibara, Mako ; Shi, Yan ; Hongo, Hiromi ; Haoyu, Wang ; Haraguchi-Kitakamae, Mai ; Shimizu, Tomohiro ; Hasegawa, Tomoka ; Yamamoto, Tomomaya ; Ishizu, Hotaka ; Li, Weisong ; Ohiro, Yoichi

OBJECTIVETo clarify the mechanism of bone anabolism induced by the parathyroid hormone-related peptide analog abaloparatide, we histochemically examined the femora of ovariectomized mice treated with abaloparatide.METHODSTwelve-week-old female C57BL/6J mice underwent ovariectomies (OVX), and were then administered either abaloparatide (30 μg/kg/day: OVX+ABL group) or vehicle (OVX group) via daily intraperitoneal injection. Femora were harvested at 0, 2, 4, and 6 weeks post-administration and subjected to micro-CT imaging, TRAP, cathepsin K, ALP, and PHOSPHO1 staining, along with calcein labeling.RESULTSIn the OVX group, trabecular number and bone volume gradually decreased over time, whereas the OVX + ABL group maintained these values to 6 weeks after OVX. The numbers of TRAP-positive/cathepsin K-reactive osteoclasts per bone surface area were similar between the OVX and OVX + ABL group, except for a temporary increase at 4 weeks in the OVX group. In the OVX group, the areas of ALP-positive osteoblastic cells and PHOSPHO1-reactive mature osteoblasts decreased, whereas in the OVX+ABL group, ALP-positive osteoblastic cells surrounded the trabeculae, and long lines of PHOSPHO1-reactive mature osteoblasts expanded to the terminal region of the trabeculae. In addition, long continuous calcein labeling was seen on slightly convex new bone, indicating modeling-based bone formation in the OVX + ABL group. The bone formation rate/bone surface ratio and the total length of modeling-based bone formation sites were higher in the OVX + ABL group than in the OVX group.CONCLUSIONAbaloparatide suppresses bone loss following ovariectomy by promoting both remodeling-based and modeling-based bone formation.

2025-03-01·Journal of Oral Biosciences

Histochemical analysis of osteoclast and osteoblast distributions on hydroxyapatite/collagen bone-like nanocomposite embedded in rat tibiae

Article

作者: Sakakibara, Mako ; Amizuka, Norio ; Hongo, Hiromi ; Yamamoto, Tomomaya ; Kikuchi, Masanori ; Li, Weisong ; Hasegawa, Tomoka ; Sato, Yoshiaki ; Cui, Jiaxin ; Liu, Xuanyu ; Haraguchi-Kitakamae, Mai ; Shi, Yan

OBJECTIVESHydroxyapatite (HAp)/collagen (Col) cylinders with laminated collagen layers were implanted into the tibial diaphysis of rats and examined histochemically to clarify how the orientation of HAp and Col bone-like nanocomposite fibers in HAp/Col blocks affects bone resorption and formation.METHODSHAp/Col fibers were synthesized and compressed into cylindrical blocks to mimic bone nanostructures. These were implanted into the cortical bone cavities of 10-week-old male Wistar rats with fiber bundles parallel to the tibial surface. The implants were histologically analyzed at 3, 5, 7, 14, and 28 days after implantation.RESULTSTRAP-positive osteoclasts appeared after 3-5 days in the lateral region of the graft, where the fiber ends were exposed, but not in the bottom region, where the HAp/Col fibers were parallel to the surface. Osteoclasts were observed in both regions by day 14. PHOSPHO1-positive osteoblasts were first detected on day 5, appearing slightly away from the cylinder laterally but directly on the bottom surface. A few osteoblasts contacted the block laterally, whereas many were observed on the new bone tissue at the bottom, between days 7 and 14. Bone formation was induced earlier in the bottom region, whereas lateral resorption was dominant. This suggested the uncoupling of bone resorption and formation in the early postimplantation stages. However, bone remodeling shifted to coupling between osteoclasts and osteoblasts throughout the cylinder by day 28.CONCLUSIONThe orientation of HAp/Col fibers in HAp/Col graft materials substantially affected the preferential induction of bone resorption or formation during the early stages of bone regeneration.

2025-03-01·Journal of Oral Biosciences

Histochemical assessment of the femora of spontaneously diabetic torii-lepr (SDT-fa/fa) rats that mimic type II diabetes

Article

作者: Liu, Xuanyu ; Yokoyama, Atsuro ; Haraguchi-Kitakamae, Mai ; Cui, Jiaxin ; Sakakibara, Mako ; Yao, Qi ; Shi, Yan ; Ishizu, Hotaka ; Hongo, Hiromi ; Shimizu, Tomohiro ; Amizuka, Norio ; Li, Weisong ; Sakaguchi, Kiwamu ; Hasegawa, Tomoka ; Tsuboi, Kanako ; Yamamoto, Tomomaya

OBJECTIVETo elucidate the mechanisms underlying diabetic osteoporosis, we conducted a comprehensive histological examination of the femora of Spontaneously Diabetic Torii-Lepr^fa (SDT-fa/fa) rats, an established model of obesity-related type 2 diabetes.MATERIALS AND METHODSFemora from 12 30-week-old male SDT-fa/fa rats and age-matched Sprague-Dawley (SD) rats (controls) were used for detailed histochemical analyses, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, tissue nonspecific alkaline phosphatase (ALP), phosphoethanolamine/phosphocholine phosphatase 1 (PHOSPHO1), dentin matrix protein 1 (DMP-1), matrix extracellular phosphoglycoprotein (MEPE), sclerostin, osteocalcin staining, silver impregnation, von Kossa staining, and micro-computed tomography (CT).RESULTSMicro-CT and hematoxylin-eosin staining demonstrated significantly reduced trabecular bone volume in the femoral metaphyses of SDT-fa/fa rats. Although the number of TRAP-positive osteoclasts per bone surface remained comparable between both groups, SDT-fa/fa rats exhibited reduced areas of ALP-positive and PHOSPHO1-reactive mature osteoblasts/BS. Silver impregnation revealed a well-organized osteocytic lacunar-canalicular system in both groups. However, immunostaining identified aberrant DMP-1 and MEPE expression localized predominantly in the lacunae in SDT-fa/fa rats and in the lacunae and canaliculi of SD rats. Additionally, intense osteocalcin and sclerostin immunoreactivity was detected in osteocytes, along with a higher proportion of osteocalcin-positive osteocytes in SDT-fa/fa rats, distinguishing them from controls.CONCLUSIONSDT-fa/fa rats displayed a significant decline in osteoblastic function and distinctive distribution patterns of osteocyte-derived peptides, suggesting that this diabetic model may manifest alterations in osteoblastic activity and the osteocytic lacunar-canalicular network.

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