Anmerkung: FRONT COVER -- RESEARCH METHODOLOGY IN THE MEDICAL AND BIOLOGICAL SCIENCES -- COPYRIGHT PAGE -- CONTENTS -- PREFACE -- ACKNOWLEDGEMENTS -- CONTRIBUTORS -- LIST OF ABBREVIATIONS AND SYMBOLS -- CHAPTER 1 PHILOSOPHY OF SCIENCE -- 1.1 Philosophy of the natural sciences -- 1.2 Philosophy of the social sciences -- References -- Further reading -- CHAPTER 2 ETHICS AND SCIENTIFIC CONDUCT -- 2.1 A brief introduction to ethics -- 2.2 Scientific conduct and misconduct -- 2.3 Misconduct and why it occurs -- 2.4 Fabrication and other forms of misconduct affecting the truth claims of scientific findings -- 2.5 Authorship issues -- 2.6 Salami, imalas and duplicate publication -- 2.7 The investigation and punishment of scientific misconduct -- References -- Further reading -- Appendix 1 -- CHAPTER 3 ETHICS IN HUMAN AND ANIMAL STUDIES -- 3.1 Introduction -- 3.2 Basic principles of human research ethics -- 3.3 International regulation -- 3.4 The ethics of animal research -- References -- Further reading -- Appendix 1 World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects -- Appendix 2 Oviedo Convention (Council of Europe, European Treaty Series 164) -- Appendix 3 Oviedo Convention - Additional Protocol Concerning Biomedical Research, Chapter I-IX (Council of Europe, European Treaty Series 195) -- CHAPTER 4 RESEARCH METHODOLOGY: STRATEGIES, PLANNING AND ANALYSIS -- 4.1 Introduction -- 4.2 Your scientific problem -- 4.3 More on scientific problems -- 4.4 Literature, methods and techniques -- 4.5 Research conditions -- 4.6 Data types -- 4.7 Techniques -- 4.8 Repeatability, reproducibility and reliability -- 4.9 Validity, effect measure and choice of statistical test -- 4.10 Experimental protocol -- 4.11 Experimental routine -- References -- Further reading. , CHAPTER 5 LITERATURE SEARCH AND PERSONAL REFERENCE DATABASES -- 5.1 Information literacy -- 5.2 Systematic literature search -- 5.3 How to formulate a query: PICO -- 5.4 Search technique -- 5.5 Methodology filters -- 5.6 Quality: critical appraisal -- 5.7 Impact factor -- 5.8 Principal bibliographic databases -- 5.9 Staying up to date -- 5.10 Medical and scientific Internet search engines -- 5.11 Personal reference databases -- References -- Further reading -- CHAPTER 6 METHODS IN MOLECULAR BIOLOGY -- 6.1 Introduction -- 6.2 Recombinant DNA technology -- 6.3 DNA and RNA: isolation, identification, synthesis and analysis -- 6.4 Practical applications of DNA/RNA technology -- 6.5 Protein analyses -- 6.6 Bioinformatics -- References -- CHAPTER 7 STRATEGIES AND METHODS OF BASIC MEDICAL RESEARCH -- 7.1 Introduction -- 7.2 Long-term goals and specific aims -- 7.3 Background and significance -- 7.4 Experimental strategies and methods -- 7.5 Pilot studies -- 7.6 Rules for basic medical research projects -- References -- Further reading -- CHAPTER 8 CLINICAL RESEARCH -- 8.1 Controlled clinical trials -- 8.2 Publication bias -- 8.3 Estimating sample size -- 8.4 'Non-inferiority' studies -- 8.5 Generalization -- References -- Guidelines -- CHAPTER 9 EPIDEMIOLOGY: CONCEPTS AND METHODS -- 9.1 Introduction -- 9.2 Definitions -- 9.3 The role of epidemiology -- 9.4 Population and sample -- 9.5 Measures of disease occurrence, association, risk and implications -- 9.6 Vital statistics -- 9.7 Study designs of epidemiological studies -- 9.8 Effect measures in epidemiological studies -- 9.9 Experimental studies and randomized control trials -- 9.10 Measurement error and sources of error -- 9.11 Tests and validity -- 9.12 Causes of disease -- 9.13 Association versus causality -- References -- Further reading -- CHAPTER 10 QUALITATIVE RESEARCH. , 10.1 Qualitative versus quantitative research -- 10.2 Using qualitative research -- 10.3 What qualitative research cannot be used for -- 10.4 Samples in qualitative studies -- 10.5 Reliability and validity -- 10.6 Ethical challenges in qualitative research -- 10.7 Qualitative data collection -- 10.8 Triangulation -- 10.9 Analyses of qualitative data -- 10.10 Releasing qualitative data -- References -- Further reading -- CHAPTER 11 STATISTICAL ISSUES -- 11.1 Introduction -- 11.2 Effect measure, hypothesis testing and confidence interval -- 11.3 Bernoulli trial -- 11.4 Comparing two proportions -- 11.5 Measures of association in 2 × 2 tables -- 11.6 Normal distribution -- 11.7 Comparison of means -- 11.8 Non-parametric methods -- 11.9 Regression analysis -- References -- Further reading -- CHAPTER 12 EVIDENCE-BASED PRACTICE AND CRITICAL APPRAISAL OF SYSTEMATIC REVIEWS -- 12.1 Introduction -- 12.2 Systematic reviews -- 12.3 Critical appraisal of a systematic review: one example -- 12.4 Summary -- References -- Further reading -- CHAPTER 13 SCIENTIFIC COMMUNICATION -- 13.1 Introduction -- 13.2 The scientific paper -- 13.3 Posters -- References -- Further reading -- CHAPTER 14 SUCCESSFUL LECTURING -- 14.1 Introduction -- 14.2 Preparing the lecture -- 14.3 Lecture content and form -- 14.4 Manuscript -- 14.5 Delivering a lecture -- Further reading -- CHAPTER 15 GUIDE TO GRANT APPLICATIONS -- 15.1 Introduction -- 15.2 Getting started -- 15.3 The postdoctoral fellow and junior scientist -- 15.4 What goes into a successful grant application? -- 15.5 The investigator-initiated research grant -- 15.6 Multiproject grants -- 15.7 International research collaborations -- 15.8 The European Union's seventh Framework Programme -- 15.9 Summary and perspective -- References -- INDEX -- A -- B -- C -- D -- E -- F -- G -- H -- I -- J -- K -- L -- M -- N -- O -- P -- Q. , R -- S -- T -- U -- V -- W -- X -- Y -- Z.

Anmerkung: Front Cover -- Research in Medical and Biological Sciences -- Copyright Page -- Contents -- List of Contributors -- Preface -- 1 Philosophy of Science -- 1.1 Introduction -- 1.2 Philosophy of the Natural Sciences -- 1.3 What Is Science? Differentiating Science from Nonscience -- 1.4 Knowledge and Truth: What is Knowledge and What Constitutes a Scientific Fact? -- 1.5 The Glue That Holds the World Together: Causation -- 1.5.1 Necessary Conditions -- 1.5.2 Sufficient Conditions -- 1.5.3 Combination of Conditions that Together are Necessary and Sufficient -- 1.5.4 Combination of Conditions that Together are Sufficient -- 1.5.5 Probabilistic Causation -- 1.5.6 Counterfactual Conditions -- 1.6 Scientific Explanation -- 1.7 Modes of Inference -- 1.8 What Science Is About -- 1.9 Scientific Rationality -- 1.10 Hypothesis Testing -- 1.10.1 Hypothetical-Deductive Method -- 1.11 The Aim of Science: Reducing Uncertainty -- 1.12 The Empirical Turn in the Philosophy of Science: Science in Society -- 1.13 Philosophy of the Social Sciences -- 1.14 Interpretation, Understanding, and Explanation -- 1.14.1 Explanation and Understanding -- 1.14.2 Interpretation -- 1.15 The Hermeneutic Circle, Horizon of Understanding, and "Double Hermeneutics" -- 1.16 Power, Ideology, and Interests -- 1.17 Validity -- 1.18 Reductionism and Emergence -- 1.19 Generalization -- Questions to Discuss -- Acknowledgments -- References -- Further Reading -- 2 Ethics and Scientific Conduct -- 2.1 Why the Current Focus on Scientific Misconduct? -- 2.2 What Do We Know About Scientific Misconduct? -- 2.3 What Is Wrong with Scientific Misconduct? -- 2.3.1 Consequentialism -- 2.3.2 Deontological Ethics -- 2.3.3 Virtue Ethics -- 2.4 Scientific Conduct and Misconduct -- 2.4.1 Internal Norms -- 2.4.2 Linkage Norms and External Norms. , 2.5 Scientific Misconduct That Affects the Truth Claims of Scientific Findings -- 2.5.1 Wrong Observations and Wrong Analysis -- 2.5.2 Plagiarism -- 2.5.3 Fabrication -- 2.6 Authorship -- 2.6.1 Exclusion from Authorship -- 2.6.2 Gift Authorship -- 2.6.3 Authorship by Coercion -- 2.6.4 Unsolicited Authorship -- 2.6.5 Ghost Authorship -- 2.6.6 Refusal to Accept Responsibility -- 2.7 Salami, Imalas, and Duplicate Publication -- 2.8 The Investigation, Prevention, and Punishment of Scientific Misconduct -- Questions to Discuss -- Appendix 1 ICMJE Recommendations on the Role of Authors and Contributors -- Why Authorship Matters -- Who Is an Author? -- Nonauthor Contributors -- References -- Further Reading -- 3 Ethics in Human and Animal Studies -- 3.1 Basic Principles of Human Biomedical Research Ethics -- 3.2 International Regulation -- 3.2.1 Consent -- 3.2.2 Inability to Consent -- 3.2.3 Randomized Controlled Trials -- 3.2.4 Vulnerable Research Participants -- 3.2.5 Epidemiological Research, "Big Data," and Biobank Research -- 3.2.6 The Role of RECs -- 3.2.7 Data Protection, Good Clinical Practice, and Other Regulations Influencing Biomedical Research Ethics -- 3.3 The Ethics of Animal Research -- 3.3.1 Animal Research and Other Human Uses of Animals -- Questions to Discuss -- References -- Further Reading -- 4 Research Strategies, Planning, and Analysis -- 4.1 Introduction -- 4.2 Identifying Scientific Problems -- 4.3 The Experimental Design -- 4.4 Data Types -- 4.5 Methods and Experimental Techniques -- 4.6 Experimental Research Checklist -- 4.7 Repeatability, Reproducibility, and Reliability -- 4.8 Multifactorial Relationships and Observational Studies -- 4.9 Validity, Effect Estimate, and Choice of Statistical Test -- 4.10 Research Protocol -- 4.11 Experimental Routines -- Acknowledgments -- Questions to Discuss -- References -- Further Reading. , 5 Literature Searches and Reference Management -- 5.1 Information Literacy -- 5.2 Literature Searches -- 5.2.1 Bibliographic Databases -- 5.2.2 Sources of Information -- 5.2.2.1 Primary Sources of Information and Primary Studies -- 5.2.2.2 Secondary Sources of Information and Secondary Studies -- 5.2.3 The Evidence Pyramid -- 5.2.4 Search Strategy -- 5.3 Establishment of a Search Query -- 5.3.1 PICO: A Focused Approach -- 5.3.2 Boolean Operator -- 5.4 Selection of Relevant Sources of Information -- 5.5 Search Techniques -- 5.5.1 Thesaurus Mapping -- 5.5.2 Federated Search -- 5.5.3 Free-Text Search -- 5.5.4 Searching by Index Term Versus Publication Type -- 5.5.5 Methodology Filters -- 5.5.5.1 PubMed Filters-Clinical Queries -- 5.5.5.2 Searching for Qualitative Research -- 5.6 Critical Assessment -- 5.6.1 Abstracts -- 5.6.2 Errata and Retracted Publications -- 5.7 Bibliometric Measures -- 5.7.1 Impact Factors -- 5.7.2 The Highly-Cited Index -- 5.8 Principal Scientific Bibliographic Databases -- 5.8.1 Medline -- 5.8.2 PubMed -- 5.8.3 EMBASE -- 5.8.4 Web of Science -- 5.8.5 BIOSIS Previews -- 5.8.6 PsycINFO -- 5.8.7 Cumulative Index to Nursing and Allied Health Literature -- 5.8.8 Cochrane Library -- 5.8.8.1 Cochrane Reviews -- 5.8.8.2 Other Reviews -- 5.8.8.3 Trials -- 5.8.8.4 Economic Evaluation -- 5.9 Staying Up to Date -- 5.9.1 Saving Search Strategies -- 5.9.2 Alert Services -- 5.9.3 Awareness Tools: Apps for Mobile Devices -- 5.9.3.1 BrowZine (for iOS and Android Devices) -- 5.9.3.2 Docphin (for iOS and Android Devices) -- 5.9.3.3 Read by QxMD (for iOS Devices, Coming on Android) -- 5.10 Medical and Scientific Internet Search Engines -- 5.10.1 Google Scholar -- 5.10.2 MacPLUS -- 5.10.3 SUMSearch2 -- 5.10.4 General Guidelines for Internet Searches -- 5.11 Finding Research Protocols and Ongoing Projects -- 5.12 Reference Management. , 5.12.1 Efficient Handling of References, Publications, and Manuscripts -- 5.12.2 EndNote -- 5.12.2.1 Settings for an EndNote Library -- 5.12.2.2 Journal Index -- 5.12.2.3 Entering References -- 5.12.2.4 Organizing References -- 5.12.2.5 Cite While You Write -- 5.12.2.6 Reference Lists-"Output Styles" -- 5.13 Open Access Publication, Copyright, and Self-Archiving -- 5.13.1 Open Access Publication -- 5.13.2 Retaining Copyright and Self-Archiving -- 5.13.3 Citing -- Questions to Discuss -- References -- Further Reading -- 6 Basic Medical Science -- 6.1 Introduction -- 6.2 Long-Term Goals and Specific Aims -- 6.3 Background and Significance -- 6.4 Experimental Strategies and Methods -- 6.5 Levels of Research-from Organisms to Cells -- 6.6 Research on Experimental Animals -- 6.7 The Three rs -- 6.8 Animal Models -- 6.9 Mouse Models for Studies of Mammalian Development and Disease -- 6.10 Legislation -- 6.11 Notes on the Use of Experimental Animals -- 6.12 Commonly Used Experimental Animals -- 6.13 Cell and Tissue Culture -- 6.14 An Overview of Selected Technical Developments -- 6.15 Applications of Cell Culture -- 6.16 Manipulation of Cultured Cells -- 6.17 Possibilities Provided by Molecular Biological Techniques -- Questions to Discuss -- References -- Further Reading -- 7 Translational Medical Research -- 7.1 Introduction -- 7.2 An Old Success Story-Aspirin -- 7.3 Research Provides a Path to Understanding Mechanisms and New Drugs -- 7.4 The Importance of Understanding Drug Metabolism-The Rise and Fall of Clopidogrel (Plavix) -- 7.5 The Need for More Translational Medical Research -- 7.6 Translational Medical Research and the Development of Orphan Drugs -- 7.7 From Rare Disorders to Common Disorders -- 7.8 Target-Based Drug Development-Aquaporins -- 7.9 Training of Investigators for Translational Medical Research. , 7.10 Collaboration Between Academia and the Pharmaceutical Industry -- Questions to Discuss -- References -- Further Reading -- 8 Clinical Research -- 8.1 Introduction -- 8.2 The Research Process-Important Steps -- 8.3 Controlled Clinical Trials -- 8.4 Drug Development -- 8.5 Clinical Trial Protocol -- 8.6 Trial Designs -- 8.7 Target Population -- 8.8 Historical Controls -- 8.9 Randomization -- 8.9.1 Stratification -- 8.9.2 Minimization -- 8.10 Blinding -- 8.11 Choice of Endpoints -- 8.12 Sample Size Estimation -- 8.12.1 Power -- 8.12.2 Sample Size Estimation for Categorical Outcomes -- 8.12.3 Sample Size Estimation for Continuous Outcomes -- 8.12.3.1 Pairs of Observations -- 8.12.3.2 Two Independent Samples (Parallel Group Trials) -- 8.12.3.3 Unequal Group Size -- 8.12.4 Sample Size Estimation Based on Precision of Estimates -- 8.12.4.1 Categorical Outcome -- 8.12.4.2 Continuous Outcome -- 8.13 Statistical Analysis -- 8.13.1 Analysis Sets -- 8.13.2 Handling of Missing Values -- 8.13.3 Analysis Strategies -- 8.13.3.1 Factorial Trials -- 8.13.3.2 Repeated Measurements -- 8.13.4 Multiple Endpoints -- 8.13.5 Interim Analyses -- 8.13.6 Subgroup Analyses -- 8.14 Personalized Medicine -- 8.15 Noninferiority Trials -- 8.16 Sources and Control of Bias -- 8.17 Generalization of Trial Results -- 8.18 Regulatory Issues -- Questions to Discuss -- Acknowledgments -- References -- 9 Epidemiology -- 9.1 Introduction -- 9.2 The Definition of Epidemiology -- 9.3 The Role of Epidemiology -- 9.3.1 Study Designs -- 9.4 Target Population, Source Population, and Study Sample -- 9.5 Disease Occurrence, Risk, Association, Importance, and Implication -- 9.5.1 Denominators, Numerators, and Time -- 9.5.2 Measures of Disease Occurrence and Risk (Incidence and Prevalence) -- 9.5.3 The Importance of Vital Statistics in an Epidemiological Setting -- 9.5.4 Mortality Rates. , 9.5.5 Cause of Death Statistics.

Anmerkung: Front Cover -- Vertebrate Skeletal Development -- Copyright -- Contents -- Contributors -- Preface -- Chapter One: Stem and progenitor cells in skeletal development -- 1. Introduction -- 2. Colony-forming unit fibroblasts (CFU-Fs) and mesenchymal/skeletal stem cells (MSCs/SSCs): A traditional definition for ... -- 3. How relevant are CFU-Fs and MSCs/SSCs to skeletal development? -- 4. In vivo lineage-tracing experiments in mice: An unambiguous approach to reveal cell fates -- 5. Endochondral bone development/Phase 1: Formation of the growth plate -- 6. Endochondral bone development/Phase 2: Formation of the perichondrium and osteoblast precursors -- 7. Endochondral bone development/Phase 3: Formation of the primary ossification center and the bone marrow cavity -- 8. Endochondral bone development/Phase 4: Formation of the postnatal growth plate and continued growth of the marrow space -- 9. Endochondral bone development/Phase 5: Establishment and maintenance of the adult bone marrow stroma -- 10. Periosteum and craniofacial sutures -- 11. Sox9 osteoblast precursors -- 12. Parathyroid hormone (PTH) action on skeletal precursors -- 13. Wnt/β-catenin signaling and cell fate decision -- 14. Conclusions and perspectives -- Acknowledgments -- References -- Chapter Two: ECM signaling in cartilage development and endochondral ossification -- 1. Introduction -- 2. Chondrogenesis and endochondral ossification -- 3. Roles of integrins in chondrogenesis and further chondrocyte maturation -- 4. Integrin downstream partners: Connecting ECM to the cell cytoskeleton -- 4.1. Focal adhesion kinase -- 4.2. Rho GTPases: Family members with different functions -- 4.3. MAP kinase cascade -- 5. Other non-integrin cell receptors -- 5.1. CD44 -- 5.2. Syndecan -- 5.3. Discoidin domain receptors -- 6. Conclusions and implications -- Acknowledgments -- References. , Chapter Three: Development of the axial skeleton and intervertebral disc -- 1. Introduction -- 2. Development of somite derived structures -- 2.1. Somitogenesis -- 2.2. Sclerotome specification -- 2.3. Resegmentation -- 2.4. Sclerotome derivatives -- 2.4.1. Vertebra -- 2.4.2. Annulus fibrosus -- 2.4.3. Tendon/ligament -- 3. Development of the nucleus pulposus from notochord -- 3.1. Formation and function of the notochord -- 3.1.1. Notochord sheath -- 3.2. Identification of notochordal and NP markers -- 3.3. Notochord-to-nucleus pulposus transition -- 3.4. Maintenance of the nucleus pulposus -- 4. Conclusions and implications -- Acknowledgments -- References -- Chapter Four: Regulatory mechanisms of jaw bone and tooth development -- 1. An overview of jaw bone and tooth development -- 2. Early development of the first pharyngeal arch -- 2.1. Cellular contributions to mandible and maxilla development -- 2.2. Molecular identity of the developing mandible and maxilla -- 3. Jaw bone development -- 3.1. Meckel´s cartilage -- 3.2. Mandibular bone osteogenesis -- 3.3. Hemifacial microsomia -- 3.4. Quantitative analysis using dynamic imaging and anatomical landmarks -- 4. Tooth development -- 4.1. Early interaction between odontogenic ectoderm and ectomesenchyme -- 4.2. Signaling regulating dentin and enamel formation -- 4.3. Tooth root development -- 4.4. Tooth and jaw bone interaction -- 4.5. Dental stem cells -- 5. Stem cells and regenerative therapies -- 5.1. Mandibular distraction osteogenesis, growth factors, and stem cell treatment -- 5.2. Dentin repair and regeneration -- 6. Conclusion and future directions -- Acknowledgments -- References -- Chapter Five: Joints in the appendicular skeleton: Developmental mechanisms and evolutionary influences -- 1. Introduction -- 2. Onset of limb synovial joint formation: The interzone. , 3. Interzone cell function and fate -- 4. Articular cartilage postnatal growth and morphogenesis -- 5. Evolutionary considerations -- 6. Conclusions and implications -- Acknowledgments -- References -- Chapter Six: BMPs, TGFβ, and border security at the interzone -- 1. Introduction -- 2. Overview of the BMP and TGFβ signaling pathways -- 3. Inhibition of BMP signaling in IZ cells is a critical step in joint formation -- 4. Genetic evidence that GDF5 has a role in joint formation -- 5. How does Gdf5 signaling direct joint formation? -- 6. TGFβ has a complex role in skeletal development -- 7. How might TGFβ signaling interfere with BMP signaling in the IZ? -- 8. Conclusions and future directions -- References -- Chapter Seven: Roles and regulation of SOX transcription factors in skeletogenesis -- 1. Introduction -- 2. Shared and distinctive features of SOX proteins -- 3. Skeletal dysmorphism due to SOX mutations -- 4. SOX genes and the control of skeletal progenitors -- 5. Roles of SOX genes in chondrogenesis -- 6. Roles of SOX genes in osteogenesis -- 7. Regulation of SOX genes and RNAs in skeletal cells -- 8. Post-translational regulation of SOX proteins in skeletal cells -- 9. Conclusions and perspectives -- Acknowledgments -- References -- Chapter Eight: Fibroblast growth factors in skeletal development -- 1. Fibroblast growth factor signaling pathways -- 2. FGF/FGFR expression -- 2.1. Expression of FGF and FGF receptors in the developing appendicularskeleton -- 2.2. Expression of FGF and FGF receptors in the developing axial skeleton -- 3. FGF signaling in growth plate chondrocytes -- 4. FGF signaling in cortical, trabecular, and intramembranous bone -- 4.1. FGFR signaling in osteoblasts -- 4.2. FGF interactions with other pathways -- 5. Mutations in FGFRs in human skeletal disease -- 5.1. Chondrodysplasia syndromes. , 5.2. Mouse models with mutations in Fgfr3 -- 5.3. FGFR signaling pathway-based therapeutic strategies -- 5.4. CATSHL syndrome (loss of function of Fgfr3) -- 5.5. Craniosynostosis syndromes -- 5.6. FGFR signaling and potential therapeutic strategies in craniosynostosis -- 6. Conclusions and perspectives -- Acknowledgments -- References -- Chapter Nine: Wnt-signaling in skeletal development -- 1. Introduction -- 1.1. Wnt-signaling -- 2. Wnt-signaling in endochondral bone formation -- 2.1. Roles of Wnt-signaling during the early steps of endochondral bone formation in the limbs -- 2.2. Effects of Wnt-signaling on proliferating chondrocytes -- 2.3. Wnt-signaling and growth plate functions -- 3. Role of Wnt signaling in osteoblast differentiation and osteoblast function -- 3.1. Wnt-signaling and osteocytes -- 4. Wnt signaling and osteoclastogenesis -- 5. Roles of Wnt-signaling in intramembranous bone formation -- 6. Wnt signaling in joint development, maintenance, and degeneration -- 7. Defects in Wnt-signaling associated with skeletal diseases -- 8. Conclusions and implications -- Acknowledgments -- References -- Chapter Ten: Gαs signaling in skeletal development, homeostasis and diseases -- 1. Introduction -- 2. Gαs signaling in human skeletal development and homeostasis -- 2.1. Skeletal diseases caused by activating mutations in the GNAS gene -- 2.2. Skeletal diseases caused by inactivating mutations in the GNAS gene -- 3. Regulation of osteoblast differentiation by Gαs signaling -- 3.1. Gαs in osteochondral progenitor cells -- 3.2. Gαs in the osteoblast lineage -- 3.3. Gαs in osteocyte lineage -- 3.4. Gαs in osteoclastogenesis -- 4. Cross talk of Gαs signaling with other signaling pathways in the skeletal system -- 4.1. Gαs is an inhibitor of Hedgehog signaling -- 4.2. Gαs signaling regulates bone through Wnt/β-catenin signaling. , 4.3. Gαs signaling and Hippo signaling -- 5. Mouse models of skeletal diseases caused by GNAS mutations -- 5.1. Mouse models of FD -- 5.1.1. Current treatment -- 5.2. POH mouse models -- 5.2.1. Current treatment options -- 6. Conclusions and implications -- Acknowledgments -- References -- Chapter Eleven: Importance of the circadian clock in tendon development -- 1. Introduction -- 2. Mammalian circadian clock -- 2.1. ``Master´´ clock -- 2.2. Cell autonomous molecular oscillator -- 3. Peripheral clocks -- 3.1. Tissue-specificity of peripheral clocks -- 3.2. Peripheral clock entrainment -- 3.3. Aging of peripheral clocks -- 4. Circadian clock regulation of tendon homeostasis -- 4.1. Tendon circadian transcriptome -- 4.2. Collagen synthesis -- 4.3. Collagen post-translational modification, folding and secretion -- 4.4. ECM remodeling -- 4.5. Ectopic calcification -- 4.6. mTOR signaling -- 4.7. TGFβ signaling -- 5. Chronotherapy for tendinopathy treatment -- 5.1. Aging of tendon clock -- 5.2. Possible methods of tendon clock entrainment -- 5.3. Implications for around-the-clock tendon care -- 6. Conclusions and implications -- Acknowledgments -- References -- Chapter Twelve: Mechanistic insights into skeletal development gained from genetic disorders -- 1. Introduction -- 2. Genetic control of patterning the appendicular skeleton -- 3. Skeletal morphogenesis: Integrated control of chondrocyte differentiation -- 4. Integrated signaling control of osteoblast differentiation and activity -- 5. Ciliopathies and the primary cilia in skeletal development -- 6. Planar cell polarity in the development of growth plate -- 7. The impact of ER stress signaling on chondrocyte differentiation -- 8. Non-coding mutations and regulatory control of skeletal development -- 9. Impacting 3D genome folding in skeletal disorders. , 10. Mechanistic insights from skeletal disorders: Impacting the path to therapy.