Key concepts Test 2 Flashcards
Making of skeletal structures
Neural crest/mesoderm undergoes mesenchymal condensation, starts from centre and grows out (intramembranous ossification -> skull/mandible/clavicle) for bone or into cartilage. The cartilage template leads to persistent cartilage of joints or is removed and turned into bone
What is intramembranous ossification and where does it occur?
Intramembranous ossification is a type of bone development in which bone tissue is created directly from mesenchymal tissue without a cartilage template. This process primarily occurs in the flat bones of the skull, mandible, and clavicle. It is crucial for the formation of the cranial bones of the skull, the clavicles, and facial bones.
< 8 weeks in development
Key steps of intramembranous ossification
Mesenchymal stem cells in the connective tissue aggregate and differentiate into osteoblasts.
Osteoblasts secrete osteoid, the organic bone matrix made of collagen and other proteins.
The osteoid matrix calcifies (hardens) when the deposited calcium salts crystallize. Bony spicules are formed
Calcified areas form trabeculae, the spongy bone which eventually fuses to form the compact bone. Spicules join trapping BV
The surface layers of undifferentiated mesenchymal cells at the periphery of the bone develop into the periosteum, which contains the bone’s blood vessels and nerves.
Endochondral ossification
Endochondral ossification is a process by which bone tissue is created from pre-existing cartilage models. This is the predominant method for the formation of the bones in the body, particularly the long bones like femur, tibia, and humerus.
> 8 weeks in development
Endochondral ossification process
- Chondrocytes mature, forming future bone, small struts calcify and enlarged chondrocytes die and leave cavities within the cartilage
- Blood vessels grow around the edge or the cartilage. Perichondrium convert to osteoblasts.
- BVs penetrate cartilage and fibroblasts migrate from BVs and differentiate into osteoblasts producing spongy bone at the centre.
- Remodelling occurs, bone shaft becomes thicker, cartilage near epiphysis is replaced by shafts of bone
- Capillaries and osteoblasts migrate into the epiphysis creating secondary ossification centres. Spherical growth
- Epiphyses filled with spongy bone, articular cartilage remains exposed to joint cavity, is reduced to thin superficial layer. Epiphyseal cartilage separates epiphysis from diaphysis.
Process of chondrogenesis
Skeletogenic mesenchymal cell develops into a condensed prechondrocyte by TGBFb and Wnt
Condensed prechondrocyte develops into an early chondrocyte by Sox9 and Sox5/6 which is from Wnt/b-catenin and Bmp respectively
How do long bones grow in length?
Long bones grow in length by the process of endochondral ossification at the epiphyseal plates. New cartilage is continuously formed on the epiphyseal side of the plate while the diaphyseal side of the plate ossifies, adding length to the bone.
Structural levels of collagen type I: collagen synthesis
Synthesis of pro-alpha chain containing Gly-X-Y repeats.
Self-assembly of three pro-alpha chains.
Procollagen triple helix formation followed by secretion into the ECM.
Cleavage of propeptide
Self-assembly into FIBRIL (see banding pattern in the EM)
Aggregation of collagen fibrils to form a collagen FIBRE
Scurvy
Vit C deficiency
Essential for production of lysyl hydroxylase, the enzyme that catalyses the hydroxylation of proline and lysine. Absence of Vit C - collagen doesn’t formed its coiled structure. Most prominent in areas with high collagen turnover (periodontal ligament)
Symptoms include rotten teeth, bleeding from all mucous membranes and bowed legs
Osteogenesis Imperfecta
Genetic disease - mutation int two genes that encode collagen type I.
Symptoms include brittle bones, weak tendons (tendinosis), abnormal skin, teeth and healing
Stickler syndrome
Type I - autosomal dominant inherited mutations in the COL2A1 gene
Type II defective formation of collagen type II
Flattened facial appearance, nearsightedness, varying hearing loss, osteoarthritis, joint pain
Aging and osteoporosis
Lose mineral and bones become less dense. Bone resorption outpaces bone formation resulting in decreased bone mass. Density and quality of bone is reduced.
Increased osteoclast activity and reduced osteoblast activity. Loss of calcium from the body and hormonal changes post menopause
Articular cartilage resist load by
Experiences compression with low amounts of tension & shear at articular surface.
Articular cartilage is a specialised form of hyaline cartilage, found at end of bones within synovial joints
Transition from a gel-like pliable tissue into the hard, ossified bone, with an intermediate of calcified cartilage acting as a protective cushion
Osteoarthritis
Affects all tissues of the joint. Presents as degeneration of articular cartilage. Low grade inflammation which is thought to contribute to ECM breakdown and viscous cycle begins.
Stiffness, joint swelling, reduced mobility. Joint replacement surgery or exercise needed
How OA progresses
Fibrillations - fraying of collagen
Collagen beneath SZ start to breakdown -> Free PG bring in H2O by bringing in more cations, increasing art cart height
Fissures develop - chondrocytes divide for futile repair and increase matrix prodution
Inflammation occurs - increased collagenase 1 and aggreanase which breaks down matrix
Bone is stiff, has pain and effusion with swelling
