Osteoblast Cell Response on Polycrystalline Diamond-Coated Additively Manufactured Scaffolds.

Additive manufacturing of metals using selective laser melting can create customized parts with various degrees of complexity and geometry for medical implants. However, challenges remain in accepting orthopedic implants due to the bio-inert surface of metal scaffolds, resulting in a lack of osseointegration. Here, we show that polycrystalline diamond (PCD) coatings on selective laser melted titanium (SLM-Ti) scaffolds can improve the cell-to-material interaction of osteoblasts.

Bone Phenotyping Approaches in Human, Mice and Zebrafish - Expert Overview of the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork").

A synoptic overview of scientific methods applied in bone and associated research fields across species has yet to be published. Experts from the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal Traits translational Network") Working Group 2 present an overview of the routine techniques as well as clinical and research approaches employed to characterize bone phenotypes in humans and selected animal models (mice and zebrafish) of health and disease. The goal is consolidation of knowledge and a map for future research.

The Thyroid Hormone Transporter MCT10 Is a Novel Regulator of Trabecular Bone Mass and Bone Turnover in Male Mice.

Thyroid hormones (TH) are essential for skeletal development and adult bone homeostasis. Their bioavailability is determined by specific transporter proteins at the cell surface. The TH-specific transporter monocarboxylate transporter 8 (MCT8) was recently reported as a regulator of bone mass in mice.

Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease.

Osteocytes are master regulators of the skeleton. We mapped the transcriptome of osteocytes from different skeletal sites, across age and sexes in mice to reveal genes and molecular programs that control this complex cellular-network. We define an osteocyte transcriptome signature of 1239 genes that distinguishes osteocytes from other cells.

Accelerating functional gene discovery in osteoarthritis.

Osteoarthritis causes debilitating pain and disability, resulting in a considerable socioeconomic burden, yet no drugs are available that prevent disease onset or progression. Here, we develop, validate and use rapid-throughput imaging techniques to identify abnormal joint phenotypes in randomly selected mutant mice generated by the International Knockout Mouse Consortium. We identify 14 genes with functional involvement in osteoarthritis pathogenesis, including the homeobox gene Pitx1, and functionally characterize 6 candidate human osteoarthritis genes in mouse models.

Role of thyroid hormones in craniofacial development.

The development of the craniofacial skeleton relies on complex temporospatial organization of diverse cell types by key signalling molecules. Even minor disruptions to these processes can result in deleterious consequences for the structure and function of the skull. Thyroid hormone deficiency causes delayed craniofacial and tooth development, dysplastic facial features and delayed development of the ossicles in the middle ear.

PYY is a negative regulator of bone mass and strength.

Objective: Bone loss in anorexia nervosa and following bariatric surgery is associated with an elevated circulating concentration of the gastrointestinal, anorexigenic hormone, peptide YY (PYY). Selective deletion of the PYY receptor Y1R in osteoblasts or Y2R in the hypothalamus results in high bone mass, but deletion of PYY in mice has resulted in conflicting skeletal phenotypes leading to uncertainty regarding its role in the regulation of bone mass. As PYY analogs are under development for treatment of obesity, we aimed to clarify the relationship between PYY and bone mass.

Slc20a2, Encoding the Phosphate Transporter PiT2, Is an Important Genetic Determinant of Bone Quality and Strength.

Osteoporosis is characterized by low bone mineral density (BMD) and fragility fracture and affects over 200 million people worldwide. Bone quality describes the material properties that contribute to strength independently of BMD, and its quantitative analysis is a major priority in osteoporosis research. Tissue mineralization is a fundamental process requiring calcium and phosphate transporters.

An atlas of genetic influences on osteoporosis in humans and mice.

Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1.

Type 2 deiodinase polymorphism causes ER stress and hypothyroidism in the brain.

Levothyroxine (LT4) is a form of thyroid hormone used to treat hypothyroidism. In the brain, T4 is converted to the active form T3 by type 2 deiodinase (D2). Thus, it is intriguing that carriers of the Thr92Ala polymorphism in the D2 gene (DIO2) exhibit clinical improvement when liothyronine (LT3) is added to LT4 therapy.

Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis.

Osteoporosis is a common disease diagnosed primarily by measurement of bone mineral density (BMD). We undertook a genome-wide association study (GWAS) in 142,487 individuals from the UK Biobank to identify loci associated with BMD as estimated by quantitative ultrasound of the heel. We identified 307 conditionally independent single-nucleotide polymorphisms (SNPs) that attained genome-wide significance at 203 loci, explaining approximately 12% of the phenotypic variance.

An Essential Physiological Role for MCT8 in Bone in Male Mice.

T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter (MCT) 8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone.

Retinol-binding protein 4 downregulation during osteogenesis and its localization to non-endocytic vesicles in human cranial suture mesenchymal cells suggest a novel tissue function.

Craniosynostosis is a developmental disorder of the skull arising from premature bony fusion of cranial sutures, the sites of skull bone growth. In a recent gene microarray study, we demonstrated that retinol-binding protein 4 (RBP4) was the most highly downregulated gene in suture tissue during the pathological process of premature bony fusion. To gain insight into the function of RBP4 in cranial sutures, we analysed primary cells cultured from human cranial suture mesenchyme.

IL-5-overexpressing mice exhibit eosinophilia and altered wound healing through mechanisms involving prolonged inflammation.

Leucocytes are essential in healing wounds and are predominantly involved in the inflammatory and granulation stages of wound repair. Eosinophils are granulocytic leucocytes and are specifically regulated by interleukin-5 (IL-5), a cytokine produced by T helper 2 (Th2) cells. To characterize more clearly the role of the IL-5 and eosinophils in the wound healing process, IL-5-overexpressing and IL-5-deficient mice were used as models of eosinophilia and eosinophil depletion, respectively.