What is the skeletal muscle developmental precursor?
How does embryonic connective tissue differ from mature connective tissue?
Embryonic: Cells are mesenchymal, high ratio of cells to ECM, ECM includes fibrous proteins embedded within hydrated, amorphous ground substance
Mature: high ratio of ECM to CT cells, consits of loose and dense fibrous CT, bone, cartilage as well as blood and lymph
What is the STFM? And what does it originate from?
Skeletal tissue forming mesenchyme (STFM)
Originates from Scleratome tissue of somites (paraxial mesoderm) and somatic mesoderm (lateral mesoderm)
What promotes mesenchyme to epithelial transformation? What cells do this?
Preskeletal condensation: epithelial-like cells of the STFM
What specific transcription factor is expressed to turn preskeletal mesenchyme into cartilage? Into bone?
Cartilage --> Sox-9
Bone --> Runx-2 (Cbfa-1)
What does Sox-9 do?
Causes preskeletal condensation to differentiate into chondroblasts and to secrete Type II collagen
Name the four main steps in carilage formation.
1. Preskeletal condensation
2. Central cells differentiate into chondroblasts
3. Chondroblasts begin to secrete carilage matrix
4. Carilage element forms; the surrounding cells form a perichondrium (fibrous capsule)
What is intramembranous ossification?
When bones form directly from a preskeletal condensation that resembles a membrane of mesenchymal cells.
What transcription factors aid in intramembranous ossification?
STFM cells exposed to low levels of BMP causing them to express Runx-2 which turns them into osteoblasts
What types of bone are usually formed by intramembranous ossification?
Superficial bones -- Flat bones
What is endochondral ossification?
Cells in STFM condensation form a carilage model of the bone.
What signaling molecules induce endochondral ossification?
Indian Hedgehog (Ihh) and sometimes Runx-2 -- chondrocytes undergo hypertrophy and secrete type X collagen and bone specific proteins
VEGF also secreted -- which stimulated blood vessel ingrowth that is accompanied by invasion of osteoblasts
What does endochondral ossification allow for?
Allows bones to grow in length d/t the presence of a cartilage growth plate (Epiphyseal plate) at one or both ends of forming bone
What are ossification centers and what are they a good measure of?
Areas of a bone primordia in which the ossification process begins
Clinically important for estabilishment of bone age -- useful index of skeletal growth and maturation, amount of epiphyseal cartilage retained within the skeleton
What are primary ossification centers?
The inital ossification center to form in a developing bone.
Where are primary ossification centers located in long bones? In flat bones?
In long bones they are usually in the shaft region
In flat bones they are usually in the center of the bone primordia
What are secondary ossification centers?
Additional centers of bone formation appearing in the prenatal, postnatal or postpuberal period.
Where are secondary ossification centers commonly located?
At the ends of long bones, the heads of ribs, the surfaces of vertebrae.
In long bones, what does closure of secondary ossification centers result in?
Disappearance of the epiphyseal plate
What is the difference between a pituitary dwarf and a achondroplastic dwarf?
Pituitary dwarf = cretinism, caused by hypothyroidism, experience mental retardation as well as skeletal and ear anomalies, bone age is younger than it should be for chonological age
Achondroplastic dwarf = autosomal dominant, assoc with mutation of Fibroblast Growth Receptor 3 (FGFR-3) interference with epiphyseal plate development results in diproportionally shortened limbs but normal sized trunk, have short fingers and accentuated lordosis, normal intelligence
How is gigantism different from acromegaly?
Depends on when hyperpituitarism occurs -- hyperpituitarism causes overproduction of growth hormone
If it occurs before epiphyseal plate closure --> gigantism
If it occurs after epiphyseal plate closure --> acromegaly (disproportionate enlargement of face, hands and feet)
How does Marfan's affect skeletal development?
Defect of production of fibrillin, a component of ECM
Individuals have spider-like elongated digits, aortic aneurysms, eye and spine abnormalities and joint hypermobility
How does mucopolysaccharidoses affect skeletal development?
Metabolic disease, affects bone formation resulting in dwarfism and bone irregularities
Absence or defect in enzyme causes accumulation of glycosaminoglycans in tissues and cells
Chronic, progressive distortinos of face and skull, thickened hairy skin, organ enlargement, altered mental devo
How does osteogenesis imperfecta?
Caused by defect in expression of Type I collagen gene
Affects skeleton, eyes, ears, joints, spine and teeth