TYPES OF BONE CELLS
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Osteocytes
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Mature bone cells
Osteoblasts
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Bone-forming cells
Osteoclasts
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Bone-destroying cells
Break down bone matrix for remodeling and release of calcium
Bone remodeling is a process by both osteoblasts and osteoclasts
TYPES OF BONE CELLS
Osteoblasts:
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located on the surface of bones.
Osteocytes
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Osteocytes
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Help to control calcium and phosphate levels in the microenvironment,
Detect mechanical forces and translate them into biologic activity-a process
called mechanotransduction
Osteoclasts
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responsible for bone resorption.
derived from the same hematopoietic progenitor cells that also give
rise to monocytes and macrophages.
The cytokines & growth factors that regulate human osteoclast
differentiation and maturation
BONE HOMEOSTASIS
BONE HOMEOSTASIS
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Bone formation and resorption are tightly coupled
OPG and RANKL oppose one another,
RANKL : OPG ratio
Systemic factors that affect RANKL and OPG expression:
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NF-κB and WNT/β-catenin signaling
Paracrine crosstalk
Proteins of bone matrix
Developmental abnormalities in bone cells, matrix, and structure:
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genetically
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manifest
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acquired in adulthood.
Dysostoses:
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Def.
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limited to
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mutations
Dysplasias:
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Mutations
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signaling molecules
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matrix components
CLASSIFICATION OF DEVELOPMENTAL ABNORMALITIES IN BONE CELLS,
MATRIX, AND STRUCTURE
Defects in nuclear proteins and transcription factors in hormones and signal transduction
extracellular structural proteins folding and degradation of macromolecules
Developmental Abnormalities in Bone Cells, Matrix, and Structure
Defects in metabolic pathways
Osteopetrosis
Decreased bone mass
Osteoporosis
Osteoclast dysfunction
Paget disease (osteitis deformans)
Abnormal mineral homeostasis
DISEASES CAUSED BY DEFECTS IN HORMONES AND SIGNAL TRANSDUCTION
MECHANISMS
Achondroplasia
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Autosomal dominant disorder
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Dwarfism.
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Mutation
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Thanatophoric dwarfism:
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the most common lethal form of dwarfism
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affecting 1/ 20,000 live births.
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It is also caused by gain-of-function mutations in FGFR3 that differ from those in
achondroplasia.
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Respiratory insufficiency due to underdeveloped thoracic cavity.
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The histologic changes
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INCREASED BONE MASS:
Gain-of-function mutations in the gene that encodes LPR5, a cell surface receptor that is
essential for the activation of the WNT/β-catenin pathway in osteoblasts.
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Endosteal hyperostosis,
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Van Buchem disease,
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Autosomal dominant osteopetrosis type 1
DISEASES ASSOCIATED WITH DEFECTS IN EXTRACELLULAR STRUCTURAL PROTEINS
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Type 1 Collagen Diseases (Osteogenesis Imperfecta/brittle bone disease)
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a phenotypically diverse disorder caused by deficiencies in the synthesis of type 1 collagen.
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It is the most common inherited disorder of connective tissue.
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It principally affects bone, & other areas rich in type 1 collagen (joints, eyes, ears, skin, and
teeth).
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Usually results from autosomal dominant mutations (over 800 have been identified) in the
genes that encode the α1 and α2 chains of collagen.
DISEASES ASSOCIATED WITH DEFECTS IN FOLDING AND DEGRADATION OF MACROMOLECULES
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Mucopolysaccharidoses:
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Definition
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Pathogenesis
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Manifestations result from
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Signs symptoms
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Osteoporosis; Morphology
Osteoporosis; Clinical features:
Severe infantile malignant osteopetrosis:
The mild autosomal dominant
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