Musculoskeletal System - Bone Development
|Embryology - 2 Dec 2021 Expand to Translate|
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The mesoderm forms nearly all the connective tissues of the musculoskeletal system, except within the head where neural crest also contributes connective tissues. Each tissue (cartilage, bone, and muscle) goes through many different mechanisms of differentiation.
The 2 key developmental processes are the initial "patterning" of bone location and then the overt "differentiation" of bone through the process of ossification. For details on specific bone differentiation in human development see Bone Development Timeline.
Bone is formed through a lengthy process involving ossification of a cartilage formed from mesenchyme. Two main forms of ossification occur in different bones, intramembranous (eg skull) and endochondrial (eg limb long bones) ossification. Ossification continues postnatally, through puberty until mid 20s. Early ossification occurs at the ends of long bones.
The two major parts of the human skeleton are the axial (80 bones in skull, vertebra, ribs, sternum) and appendicular (126 bones in limbs, shoulders, pelvis) skeletons.
Musculoskeletal and limb abnormalities are one of the largest groups of congenital abnormalities.
Some Recent Findings
|More recent papers|
This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
Search term: Bone Embryology
<pubmed limit=5>Bone Embryology</pubmed>
Adult Human Skeleton
- The Developing Human: Clinically Oriented Embryology (8th Edition) by Keith L. Moore and T.V.N Persaud - Moore & Persaud Chapter 15 the skeletal system
- Larsen’s Human Embryology by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 11 Limb Dev (bone not well covered in this textbook)
- Before we Are Born (5th ed.) Moore and Persaud Chapter 16,17: p379-397, 399-405
- Essentials of Human Embryology Larson Chapter 11 p207-228
- Identify the components of a somite and the adult derivatives of each component.
- Give examples of sites of (a) endochondral and (b) intramembranous ossification and to compare these two processes.
- Identify the general times (a) of formation of primary and (b) of formation of secondary ossification centres, and (c) of fusion of such centres with each other.
- Briefly summarise the development of the limbs.
- Describe the developmental abnormalities responsible for the following malformations: selected growth plate disorders; congenital dislocation of the hip; scoliosis; arthrogryposis; and limb reduction deformities.
Below is a very brief overview using simple figures of 3 aspects of early musculoskeletal development. More detailed overviews are shown on other notes pages Mesoderm and Somite, Vertebral Column, Limb in combination with serial sections and Carnegie images.
|Cells migrate through the primitive streak to form mesodermal layer. Extraembryonic mesoderm lies adjacent to the trilaminar embryo totally enclosing the amnion, yolk sac and forming the connecting stalk.|
|Paraxial mesoderm accumulates under the neural plate with thinner mesoderm laterally. This forms 2 thickened streaks running the length of the embryonic disc along the rostrocaudal axis. In humans, during the 3rd week, this mesoderm begins to segment. The neural plate folds to form a neural groove and folds.|
|Segmentation of the paraxial mesoderm into somites continues caudally at 1 somite/90minutes and a cavity (intraembryonic coelom) forms in the lateral plate mesoderm separating somatic and splanchnic mesoderm.
Note intraembryonic coelomic cavity communicates with extraembryonic coelom through portals (holes) initially on lateral margin of embryonic disc.
|Somites continue to form. The neural groove fuses dorsally to form a tube at the level of the 4th somite and "zips up cranially and caudally and the neural crest migrates into the mesoderm.|
- Secondary ossification centres develop in the cartilage epiphysis of the long bones.
- No medulary cavity forms in a secondary ossification center.
- Appears late in fetal development.
- Used as a marker for term development if a secondary ossification centre present in either: head of femur, head of tibia, of head of humerus.
- The last secondary centre to appear is the clavical medial epiphysis, that does not develop until 18 or 20 years.
- (dense) no spaces or hollows in the bone matrix visible to the eye.
- forms the thick-walled tube of the shaft (or diaphysis) of long bones, which surrounds the marrow cavity (or medullary cavity). A thin layer of compact bone also covers the epiphyses of long bones.
- (cancellous or spongy bone) consists of delicate bars (spicules) and sheets of bone, trabeculae
- branch and intersect to form a sponge-like network
- ends of long bones (or epiphyses) consist mainly of trabecular bone.
Connective tissue covering the surface of bone (except articular surfaces). The embryonic origin of this layer is still controversial.
Connective tissue lining inner surface of bone.
- Appositional growth occurs at either the periosteum (outer surface), or the endosteum (inner surface).
- Osteoblasts secrete osteoid, a pre-bone material composed mainly of type I collagen that becomes mineralized.
- Early bone matrix deposited in development and during repair is woven rather than lamellar in appearance and structure.
- In development, there are 2 distinct types of bone formation (intramembranous and endochondral)
- derive from osteogenic stem cells the osteoprogenitor cells that differentiate to form pre-osteoblast then osteoblasts maturing to an osteocyte
- osteoprogenitor cells - "resting cell" line the inner and outer surfaces of bone
- mature bone-forming cells embedded in lacunae within the bone matrix
- osteoblasts and osteocytes - secrete organic matrix of bone (osteoid), converted into osteocytes when become embedded in matrix (which calcifies soon after deposition)
- bone-resorbing multinucleated macrophage-like cells
- origin- fusion of monocytes or macrophages, Blood macrophage precursor, Attach to bone matrix
- seal a small segment of extracellular space (between plasma membrane and bone surface), HCl and lysosomes secreted into this space by osteoclasts dissolves calcium phosphate crystals (give bone rigidity and strength)
- Resorptive bay - (Howship's lacuna) shallow bay lying directly under an osteoclast.
- do not mistake for megakaryocytes, found in bone marrow not associated with bone matrix.
- megakaryocytes are also multi-niucleated and form platelets
- red marrow - mainly haematopoietic (myeloid) tissue, newborn has all red marrow
- yellow marrow - mainly fat cells, found in diaphysis region of long bones
- stromal cells - all other support cells not involved in haematopoiesis
- Links: Blood Development
Marrow stroma components:
- osteoblasts - enclose the marrow compartment in bone tissue.
- endothelial and smooth muscle cells - organized into a complex vascular network composed of arterioles, capillaries, sinusoids, and a large central vein.
- nerves - sensory and sympathetic nerve fibres, glia, and perineural cells that innervate the marrow compartment to form a neural network.
- adipocytes - support metabolic functions of the bone marrow.
- stromal cells - support haematopoiesis and retain skeletal potential.
The bone matrix has 2 major components.
- Organic portion composed of mainly collagen Type 1 (about 95%) and amorphous ground substance.
- Inorganic portion (50% dry weight of the matrix) composed of hydroxyapatite crystals, calcium, phosphorus, bicarbonate, nitrate, Mg, K, Na.
- storage calcium and phosphate
- regulate blood calcium levels
- also called osteons
- Volkmann's canals - interconnect Haversian systems
- concentric - surrounding each Haversian System
- interstitial - bony plates that fill in between the haversian systems.
- circumferential - layers of bone that underlie the periosteum and endosteum
- osteocytes extending cytoplasmic processes into canaliculi
- Additional Histology images: low | medium | high
Most of the bony skeleton forms by this process, that replaces a developmental cartilage template with bone.
See also Bone Histology
- Links: Blue Histology - endochondral | Dev Biology - endochondral ossification | endochondral ossification animation
Only specific parts of the skeleton form by this process, where bone forms by direct ossification of mesenchyme without a pre-existing cartilage template.
This process occurs in regions of the skull and the clavicle.
See also Bone Histology
Human Fetal Head (12 week)
The transcription factors Runx2 and Runx3 are essential for chondrocyte maturation, while Runx2 and Osterix are essential for osteoblast differentiation.
Osterix (OSX) encodes a transcription factor containing three Cys2-His2 zinc-finger DNA-binding domains at its C terminus that has been shown to be essential for bone formation.
Osteogenesis Imperfecta (OI, brittle bone disease) originally described as a collagen 1 gene mutation, but can have several different genetic causes and can be classified into eight different types (I-VIII).
- COL1A1 and COL1A2 mutations
- CRTAP and LEPRE1 mutations, in severe/lethal and recessively inherited osteogenesis imperfecta
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- BONE is an interdisciplinary forum for the rapid publication of original articles and reviews on basic, translational, and clinical aspects of bone and mineral metabolism.
- canaliculus - (plural, canaliculi) small channel in the bone matrix in which an osteocyte process lies and communicates with other osteocytes and the Haversian canal.
- diaphysis - anatomical term that refers to the shaft of long bones.
- epiphysis - anatomical term that refers to the expanded ends of long bones.
- haematopoiesis (Greek, haima = "blood"; poiesis = "to make") the process of blood cell formation. In the adult, this occurs only in the bone marrow. In the embryo this occurs in other locations (yolk sac, liver, spleen, thymus) until bone develops.
- Haversian canal - the central canal of an osteon (Haversian system) in compact bone, within which blood vessels and nerves travel throughout the bone.
- Haversian system - (osteon) the historic name for the functional unit of compact bone. Consists of a central canal (Haversian canal) surrounded by lamellar bone matrix within which osteocytes reside.
- Howship's lacuna - (resorptive bay) the historic name for the shallow bay or cavity lying directly under an osteoclast. This is the site of bone matrix resorption.
- lacuna - (Latin, lacuna = “ditch, gap” diminutive form of lacus = “lake”) lacunae is the plural, cavity in bone or cartilage for cell.
- lamellar bone - the highly organized strong bone matrix deposited in concentric sheets with a low proportion of osteocytes. Many collagen fibers parallel to each other in the same layer.
- metaphysis - anatomical term that connecting region, that lies between the diaphysis and epiphysial line.
- osteon - (Haversian system) the functional unit of compact bone. Consists of a central canal (Haversian canal) surrounded by lamellar bone matrix within which osteocytes reside.
- resorptive bay - (Howship's lacuna) the shallow bay or cavity lying directly under an osteoclast. This is the site of bone matrix resorption.
- suture - in the skull a form of articulation where the contiguous margins of the bones are united by a thin layer of fibrous tissue.
- woven bone - the first deposited weaker bone matrix with many osteocytes and a matrix disorganized structure. Replaced by lamellar bone. Seen in developing, healing and bone disease.
- medullary cavity - (bone marrow) refers to the cavity within the bone, that is lined with cells and filled with bone marrow. in the adult, this can also be identified as either red or yellow marrow.
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- Virtual Slidebox of Histology (USA) Skeletal system
- e-radiography Ossification
- UWA Blue Histology bone
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Cite this page: Hill, M.A. (2021, December 2) Embryology Musculoskeletal System - Bone Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Musculoskeletal_System_-_Bone_Development
- © Dr Mark Hill 2021, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G