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PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures.

ABSTRACT: Phosphatases are essential for the mineralization of the extracellular matrix within the skeleton. Their precise identities and functions however remain unclear. PHOSPHO1 is a phosphoethanolamine/phosphocholine phosphatase involved in the generation of inorganic phosphate for bone mineralization. It is highly expressed at sites of mineralization in bone and cartilage. The bones of Phospho1(-/-) mice are hypomineralized, bowed and present with spontaneous greenstick fractures at birth. In this study we show that PHOSPHO1 is essential for mechanically competent mineralization that is able to withstand habitual load. Long bones from Phospho1(-/-) mice did not fracture during 3-point bending but deformed plastically. With dynamic loading nanoindentation the elastic modulus and hardness of Phospho1(-/-) tibiae were significantly lower than wild-type tibia. Raman microscopy revealed significantly lower mineral:matrix ratios and lower carbonate substitutions in Phospho1(-/-) tibia. The altered dihydroxylysinonorleucine/hydroxylysinonorleucine and pyridinoline/deoxypyridinoline collagen crosslink ratios indicated possible changes in lysyl hydroxylase-1 activity and/or bone mineralization status. The bone formation and resorption markers, N-terminal propeptide and C-terminal telopeptide of Type I collagen, were both increased in Phospho1(-/-) mice and this we associated with increased bone remodeling during fracture repair or an attempt to remodel a mechanically competent bone capable of withstanding physiological load. In summary these data indicate that Phospho1(-/-) bones are hypomineralized and, consequently, are softer and more flexible. An inability to withstand physiological loading may explain the deformations noted. We hypothesize that this phenotype is due to the reduced availability of inorganic phosphate to form hydroxyapatite during mineralization, creating an undermineralized yet active bone.

SUBMITTER: Huesa C

PROVIDER: S-EPMC3078982 | biostudies-other | 2011 May

REPOSITORIES: biostudies-other

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PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures.

Huesa Carmen C Yadav Manisha C MC Finnilä Mikko A J MA Goodyear Simon R SR Robins Simon P SP Tanner K Elizabeth KE Aspden Richard M RM Millán José Luis JL Farquharson Colin C

Bone 20110125 5

Phosphatases are essential for the mineralization of the extracellular matrix within the skeleton. Their precise identities and functions however remain unclear. PHOSPHO1 is a phosphoethanolamine/phosphocholine phosphatase involved in the generation of inorganic phosphate for bone mineralization. It is highly expressed at sites of mineralization in bone and cartilage. The bones of Phospho1(-/-) mice are hypomineralized, bowed and present with spontaneous greenstick fractures at birth. In this st ...[more]

PMID: 21272676

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Project description:BackgroundIndividuals with Autism Spectrum Condition (ASC) are characterized by atypicalities in social interactions, compared to Typically Developing individuals (TD). The social motivation theory posits that these difficulties stem from diminished anticipation, reception, and/or learning from social rewards. Although learning from socioemotional outcomes is core to the theory, studies to date have been sparse and inconsistent. This possibly arises from a combination of theoretical, methodological and sample-related issues. Here, we assessed participants' ability to develop a spontaneous preference for actions that lead to desirable socioemotional outcomes (approaching/avoiding of happy/angry individuals, respectively), in an ecologically valid social scenario. We expected that learning abilities would be impaired in ASC individuals, particularly in response to affiliative social feedback.MethodWe ran an online social reinforcement learning task, on two large online cohorts with (n = 274) and without (n = 290) ASC, matched for gender, age and education. Participants had to indicate where they would sit in a waiting room. Each seat was associated with different probabilities of approaching/avoiding emotional individuals. Importantly, the task was implicit, as participants were not instructed to learn, and emotional expressions were never mentioned. We applied both categorical analyses contrasting the ASC and TD groups and dimensional factor analysis on affective questionnaires.ResultsContrary to our hypothesis, participants showed spontaneous learning from socioemotional outcomes, regardless of their diagnostic group. Yet, when accounting for dimensional variations in autistic traits, as well as depression and anxiety, two main findings emerged among females who failed to develop explicit learning strategies: (1) autism severity in ASC correlated with reduced learning to approach happy individuals; (2) anxiety-depression severity across both ASC and TD participants correlated with reduced learning to approach/avoid happy/angry individuals, respectively.ConclusionsImplicit spontaneous learning from socioemotional outcomes is not generally impaired in autism but may be specifically associated with autism severity in females with ASC, when they do not have an explicit strategy for adapting to their social environment. Clinical diagnosis and intervention ought to take into account individual differences in their full complexity, including the presence of co-morbid anxiety and depression, when dealing with social atypicalities in autism.

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PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures.

Publications

PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures.

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