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Wnts' fashion statement: from body stature to dysplasia.

ABSTRACT: Bone is constantly being made and remodeled to maintain bone volume and calcium homeostasis. Even small changes in the dosage, location and duration of int/Wingless (Wnt) signaling affect skeletal development and homeostasis. Wnt/?-catenin signaling controls cell fate determination, proliferation and survival by affecting a balance between bone-forming osteoblast and bone-resorbing osteoclast cell differentiation. During early skeletal development, Wnt/?-catenin signaling is required in directing mesenchymal progenitor cells toward the osteoblast lineage. Later, Wnt/?-catenin in chondrocytes of the growth plate promotes chondrocyte survival, hypertrophic differentiation and endochondral ossification. Gain- or loss-of-function mutations in the Wnt signaling components are causally linked to high or low bone mass in mice and humans. Inactivation of Wnt/?-catenin signaling leads to imbalance between bone formation and resorption because of accelerated osteoclastogenesis due to decline in the levels of osteoprotegerin (OPG) secreted by osteoblasts or directly via Frizzled 8 (Fzd8). In this review, we provide a landscape of the Wnt pathway components in influencing progenitor cell differentiation toward osteoblasts or osteoclasts under physiological conditions as well as pathological disorders resulting in various skeletal dysplasia syndromes.

SUBMITTER: Malhotra D

PROVIDER: S-EPMC4078412 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Wnts' fashion statement: from body stature to dysplasia.

Malhotra Deepti D Yang Yingzi Y

BoneKEy reports 20140611

Bone is constantly being made and remodeled to maintain bone volume and calcium homeostasis. Even small changes in the dosage, location and duration of int/Wingless (Wnt) signaling affect skeletal development and homeostasis. Wnt/β-catenin signaling controls cell fate determination, proliferation and survival by affecting a balance between bone-forming osteoblast and bone-resorbing osteoclast cell differentiation. During early skeletal development, Wnt/β-catenin signaling is required in directin ...[more]

PMID: 24991404

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Project description:PurposeStature at a particular age can be considered the cumulative result of growth during a number of preceding growth trajectory periods. We investigated whether height and weight growth trajectories from birth to age 10 years were related to refractive error at ages 11 and 15 years, and eye size at age 15 years.DesignProspective analysis in a birth cohort.ParticipantsChildren participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) U.K. birth cohort (minimum N = 2676).MethodsGrowth trajectories between birth and 10 years were modeled from a series of height and weight measurements (N = 6815). Refractive error was assessed by noncycloplegic autorefraction at ages 11 and 15 years (minimum N = 4737). Axial length (AXL) and radius of corneal curvature were measured with an IOLMaster (Carl Zeiss Meditec, Welwyn Garden City, U.K.) at age 15 years (minimum N = 2676). Growth trajectories and an allelic score for 180 genetic variants associated with adult height were tested for association with refractive error and eye size.Main outcome measuresNoncycloplegic autorefraction at ages 11 and 15 years, and AXL and corneal curvature at age 15 years.ResultsHeight growth trajectory during the linear phase between 2.5 and 10 years was negatively associated with refractive error at 11 and 15 years (P<0.001), but explained <0.5% of intersubject variation. Height and weight growth trajectories, especially shortly after birth, were positively associated with AXL and corneal curvature (P<0.001), predicting 1% to 5% of trait variation. Height growth after 2.5 years was not associated with corneal curvature, whereas the association with AXL continued up to 10 years. The height allelic score was associated with corneal curvature (P = 0.03) but not with refractive error or AXL.ConclusionsUp to the age of 10 years, shared growth mechanisms contribute to scaling of eye and body size but minimally to the development of myopia.Financial disclosure(s)The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Project description:Body size is a central determinant of a species' biology and adaptive strategy, but the number of reliable estimates of hominin body mass and stature have been insufficient to determine long-term patterns and subtle interactions in these size components within our lineage. Here, we analyse 254 body mass and 204 stature estimates from a total of 311 hominin specimens dating from 4.4?Ma to the Holocene using multi-level chronological and taxonomic analytical categories. The results demonstrate complex temporal patterns of body size variation with phases of relative stasis intermitted by periods of rapid increases. The observed trajectories could result from punctuated increases at speciation events, but also differential proliferation of large-bodied taxa or the extinction of small-bodied populations. Combined taxonomic and temporal analyses show that in relation to australopithecines, early Homo is characterized by significantly larger average body mass and stature but retains considerable diversity, including small body sizes. Within later Homo, stature and body mass evolution follow different trajectories: average modern stature is maintained from ca 1.6?Ma, while consistently higher body masses are not established until the Middle Pleistocene at ca 0.5-0.4?Ma, likely caused by directional selection related to colonizing higher latitudes. Selection against small-bodied individuals (less than 40?kg; less than 140?cm) after 1.4?Ma is associated with a decrease in relative size variability in later Homo species compared with earlier Homo and australopithecines. The isolated small-bodied individuals of Homo naledi (ca 0.3?Ma) and Homo floresiensis (ca 100-60?ka) constitute important exceptions to these general patterns, adding further layers of complexity to the evolution of body size within the genus Homo. At the end of the Late Pleistocene and Holocene, body size in Homo sapiens declines on average, but also extends to lower limits not seen in comparable frequency since early Homo.

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Wnts' fashion statement: from body stature to dysplasia.

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Wnts' fashion statement: from body stature to dysplasia.

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