Analysis of Association between Morphometric Parameters of Growth Plate and Bone Growth of Tibia in Mice and Humans

Wilson, Kimberly; Usami, Yu; Hogarth, Danielle A.; Scheiber, Amanda L.; Tian, Hongying; Oichi, Takeshi; Wei, Yulong; Qin, Ling; Otsuru, Satoru; Toyosawa, Satoru; Iwamoto, Masahiro; Abzug, Joshua M.; Enomoto‐Iwamoto, Motomi

doi:10.1177/1947603519900800

Cited by 9 publications

(4 citation statements)

References 47 publications

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“…Specialization of vascular morphology within the long bones initiates at postnatal day 6, with metaphyseal capillaries acquiring a column-like structure and diaphyseal capillaries forming a sinusoidal network 28 . Murine long bone growth evolves rapidly until P14, reaching a steady growth phase between P14 and P42 29 , 30 . This is in accordance with the already described rapid decline of the metaphyseal vessels over the first 4 weeks postnatally 7 .…”

Section: Discussionmentioning

confidence: 99%

Endothelial SMAD1/5 signaling couples angiogenesis to osteogenesis in juvenile bone

Lang,

Benn,

Collins

et al. 2024

Commun Biol

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Skeletal development depends on coordinated angiogenesis and osteogenesis. Bone morphogenetic proteins direct bone formation in part by activating SMAD1/5 signaling in osteoblasts. However, the role of SMAD1/5 in skeletal endothelium is unknown. Here, we found that endothelial cell-conditional SMAD1/5 depletion in juvenile mice caused metaphyseal and diaphyseal hypervascularity, resulting in altered trabecular and cortical bone formation. SMAD1/5 depletion induced excessive sprouting and disrupting the morphology of the metaphyseal vessels, with impaired anastomotic loop formation at the chondro-osseous junction. Endothelial SMAD1/5 depletion impaired growth plate resorption and, upon long-term depletion, abrogated osteoprogenitor recruitment to the primary spongiosa. Finally, in the diaphysis, endothelial SMAD1/5 activity was necessary to maintain the sinusoidal phenotype, with SMAD1/5 depletion inducing formation of large vascular loops and elevated vascular permeability. Together, endothelial SMAD1/5 activity sustains skeletal vascular morphogenesis and function and coordinates growth plate remodeling and osteoprogenitor recruitment dynamics in juvenile mouse bone.

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Section: Discussionmentioning

confidence: 99%

Endothelial SMAD1/5 signaling couples angiogenesis to osteogenesis in juvenile bone

Lang,

Benn,

Collins

et al. 2024

Commun Biol

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“…Distinct vascular morphology has been described starting at postnatal day 6 with metaphyseal capillaries (type H vessel) showing a column-like structure and diaphyseal capillaries (type L vessel) forming a sinusoidal network ( 26 ). Murine long bone growth evolves rapidly until P14, reaching a steady growth phase between P14 and P42 ( 27, 28 ). This is in accordance with the already described rapid decline of the Type H vessel over the first 4 weeks postnatally ( 4 ).…”

Section: Discussionmentioning

confidence: 99%

Endothelial SMAD1/5 signaling couples angiogenesis to osteogenesis during long bone growth

Lang

Benn

Wolter

et al. 2023

Preprint

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Skeletal development depends on coordinated angiogenesis and osteogenesis. Bone morphogenetic proteins direct bone development by activating SMAD1/5 signaling in osteoblasts. However, the role of SMAD1/5 in skeletal endothelium is unknown. Here, we found that endothelial cell-conditional SMAD1/5 depletion in juvenile mice caused metaphyseal and diaphyseal hypervascularity, resulting in altered cancellous and cortical bone formation. SMAD1/5 depletion induced excessive sprouting, disrupting the columnar structure of the metaphyseal vessels and impaired anastomotic loop morphogenesis at the chondro-osseous junction. Endothelial SMAD1/5 depletion impaired growth plate resorption and, upon long term depletion, abrogated osteoprogenitor recruitment to the primary spongiosa. Finally, in the diaphysis, endothelial SMAD1/5 activity was necessary to maintain the sinusoidal phenotype, with SMAD1/5 depletion inducing formation of large vascular loops, featuring elevated endomucin expression, ectopic tip cell formation, and hyperpermeability. Together, endothelial SMAD1/5 activity sustains skeletal vascular morphogenesis and function and coordinates growth plate remodeling and osteoprogenitor recruitment dynamics during bone growth.

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“…The in situ expression of leptin receptor at the GP supported that leptin directly affected the GP. GP thickness was an important histological marker for the longitudinal bone growth ( 34 ). Here, we focused on the GPs and found that the femoral GP was thinner than that of WT mice, and the spinal GP was thicker than that of WT mice.…”

Section: Discussionmentioning

confidence: 99%

The Role of Estrogen Receptor α in Response to Longitudinal Bone Growth in ob/ob Mice

Jin

Guo

et al. 2021

Front. Endocrinol.

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The absence of leptin results in contrasting growth pattern of appendicular and axial bone growth in ob/ob mice. Endochondral bone formation is an important procedure of growth plate determining the bone growth, where this procedure is also regulated by estrogen and its receptor (ER) signaling pathway. The present study is undertaken to explore the roles of ERs in regulating the different growth patterns in ob/ob mice. In this study, C57BL/6 female mice were used as wild-type (WT) mice; ob/ob mice and WT mice were age-matched fed, and bone length is analyzed by X-ray plain film at the 12 weeks old. We confirm that ob/ob mice have shorter femoral length and longer spine length than WT mice (p < 0.05). The contrasting expression patterns of chondrocyte proliferation proteins and hypertrophic marker proteins are also observed from the femur and spinal growth plate of ob/ob mice compared with WT mice (p < 0.01). Spearman’s analysis showed that body length (axial and appendicular length) is positively related to the expression level of ERα in growth plate. Three-week-old female ob/ob mice are randomized divided into three groups: 1) ob/ob + ctrl, 2) ob/ob + ERα antagonist (MPP), and 3) ob/ob + ERβ antagonist (PHTPP). Age-matched C57BL/6 mice were also divided into three groups, same as the groups of ob/ob mice. MPP and PHTPP were administered by intraperitoneal injection for 6 weeks. However, the results of X-ray and H&E staining demonstrate that leptin deficiency seems to disturb the regulating effects of ER antagonists on longitudinal bone growth. These findings suggested that region-specific expression of ERα might be associated with contrasting phenotypes of axial and appendicular bone growth in ob/ob mice. However, ER signaling on longitudinal bone growth was blunted by leptin deficiency in ob/ob mice, and the underlying association between ERs and leptin needs to be explored in future work.

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Analysis of Association between Morphometric Parameters of Growth Plate and Bone Growth of Tibia in Mice and Humans

Cited by 9 publications

References 47 publications

Endothelial SMAD1/5 signaling couples angiogenesis to osteogenesis in juvenile bone

Endothelial SMAD1/5 signaling couples angiogenesis to osteogenesis in juvenile bone

Endothelial SMAD1/5 signaling couples angiogenesis to osteogenesis during long bone growth

The Role of Estrogen Receptor α in Response to Longitudinal Bone Growth in ob/ob Mice

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