Bone Formation and Growth

Steps of endochondral ossification

1) clay form that bone has to work with - mesenchymal cells first develop into chondroblasts to form the hyaline cartilage model 2) repeated cell division that grows outward towards ends of bones - chondroblasts continue to divide - chondrocytes begin to hypertrophy (get big) - chondrocytes are getting too excited and big and stop secreting collagen (normal matrix) after that hypertrophy - they start secreting alkaline phosphate, an enzyme that is essential for mineral deposition - as they hypertrophy, they attract minerals that cause their matrix to calcify - when matrix calcify, chondrocytes can't get nutrients anymore so they start to die 3) as they die, they give off another chemical signal, which is the angiogenesis factor (blood vessel growth) - sends signal around the body that cause the ingrowth of nutrient artery (one of the blood vessels important for bone growth) - nutrient artery comes in and there is blood supply to cartilage model, which brings in osteoblasts - when nutrient artery bursts through the model, the primary ossification center forms - when osteoblasts arrive, the start of osteoossification cdnter - spongy bone I'd formed by osteoblasts in interior of bone - periosteum forming from perichondrium cells 4) blood vessel brought osteoblasts as well - as osteoblasts make spongy bone on interior of this model, osteoclasts follow up to carve away at spongy bone soo that we have a hollow medullary cavity that is lined with spongy bone in the interior near the ends - osteoclasts and blasts stop and leave the calcified ECM with some uncalcified ECM above it - this area is where bones grow in length (cartilage cells still present in this area); grow plate 5) blood vessels that enter the diaphysis can't get into the epiphysis m- second supply of blood vessels, the epiphyseal artery and vein, penetrate cartilage at epiphysis - brings osteoblasts with it and secret bone matrix and form spongy bone again - spongy bone isn't carved away by osteoclast because they can't get into the epiphysis -- development of secondary ossification centers (in epiphysis of bone) 6) some spongy bone on end with medullary cavity is mostly hallow - in epiphyseal plate of cartilage left with spongy bone in epiphysis covered all with articular cartilage that is left over - articular cartilage left on surface ends, no bone tissue replaces those areas -- both made of hyaline cartilage These are done by the time we're born

Bone forms in 4 situations

1) during embryo logical and fetal development (initial formation) 2) when bones grow before adulthood (infancy, childhood, adolescence) 3) when bones remodel (exercise more, gain weight, gain muscle) 4) when fractures heal

Steps of intramembranous ossification

1) mesenchymal cells differentiate into osteoprogenitor cells, which transform into osteoblasts. This forms a primary ossification center. these osteoblasts secrete/ calcify osteoid (extracellular matrix) until they are surrounded by it. Surround the collagen fibers that were already in the dense irregular tissue. 2) canaliculi are formed by projections of the osteoblasts. Allow cells to communicate with each other. calcification occurs when secretion of ECM stops and osteoblasts are now trapped in place ➡️ osteocytes. Within a few days, calcium and other mineral salts are deposited which harden the matrix - osteoblasts wills surround ossification center on the exterior ➡️ develops into periosteum of bone -release chemical signals that attract the deposition of minerals; cause ECM to calcify 3) line of osteoblasts will continue to differentiate outward, thickening surrounding blood vessels until visible trabeculae are formed. The spaces surrounding the blood vessels become filled with red bone marrow. as the bone ECM forms, it develops into trabeculae that fuse with one another to form spongy bone around the network of blood vessels in the tissue. This is how trabeculae gets its shape. All matrix will fuse together to create trabeculae and that's what gives spongy bone its appearance. The connective tissue associated with blood vessels in the trabeculae differentiates into red bone marrow. 4) external mesenchyme condenses at the periphery to form the periosteum, which will secrete new bone cells to form the compact bone tissue surrounding it, which adds stability (replaced by a thin layer of compact bone). - mesenchymal cells condensing along outer periosteum and will develop periosteum, which is dense irregular connective tissue

Endochondral ossification

Bone arise from hyaline cartilage model; make cartilage first in the shape that bone will be and bone tissue will replace it Replaces hyaline cartilage (growing in length and size) with bone in developing embryo and fetus Formation of long bones and natural healing of bones from fractures

Bone degeneration

Bone degenerates quickly Up to 1/3 of bone mass can be lost in a few weeks of inactivity

The aging skeletal system

Bones become thinner and weaker with age - osteopenia, normal expected loss of bone density with age, begins btwn ages 30 and 40 - women lose 8% of bone mass per decade, men 3% The epiphyses, vertebrae, and jaws are most affected - resulting in fragile limbs - reduction in height - tooth loss Spongy bone degrades faster than compact bone (wrist, hip)

Bone's role in calcium homeostasis

Bones store 99% of the body's calcium The parathyroid gland secretes the parathyroid hormone when calcium levels drop - osteoclasts are stimulated to increase bone resorption and calcium is released - PTH also stimulates the production of calcitriol (vitamin d) by the kidneys to increase calcium absorption in the intestines Osteoclasts break down the matrix

Effects of exercise on bone

Mineral recycling allows bones to adapt to stress Heavily stressed bones become thicker and stronger

Intramembranous ossification

Rise from connective tissue/ mesenchymal cells Simpler of the two Flat bones of the skull, most facial bones, mandible, collarbones Occurs in utero and after fractures *Bone develop from dense irregular connective tissue

Osteoporosis

Severe bone loss Affects normal function over age 45, occurs in - 29% of women - 18% of men

Bone remodeling

The adult skeleton maintains itself; replaces mineral reserves; recycled and renews bone matrix; involves osteocytes, osteoblasts, and clasts - turnover rate varies - if deposition is greater than removal, bones get stronger - if removal is faster than replacement, bones get weaker

Bone growth in thickness

Bones thicken thanks to the cooperative action of osteoblasts and clasts Some have thicker layer of compact bone on outside than others (lower body) Bones will thicken from periosteum via ap positional growth Bones will grow from periosteum layer outward 1) cells of periosteum differentiating into osteoblasts; secrete collagen fibers and other things that make up ECM; bone matrix being laid down; always happen around blood vessel of periosteum; start to form a periosteal ridge; secrete matrix around blood vessel 2) periosteal ridges being fused to form an osteon, form an Endosteum lined tunnel 3) osteoblasts in Endosteum (inner layer) will continue to secrete matrix outward, build new concentric lamellae inward toward center of tunnel, forming a new osteon 4) bone grows outward as osteoblasts in periosteum build new circumferential lamellae. Osteon formation repeats as new periosteal ridges fold over blood vessels. Arranged in same direction to resist compressive forces As bones grow in thickness, bone is getting stronger and heavier Osteoclasts on inside will break down tissue from inside outward Osteoclasts keep carving out medullary cavity behind it

Exercise, hormones, and nutrition

Calcitriol - made in kidneys - helps absorb calcium and phosphorus from digestive tract - synthesis requires vitamin d3 Growth hormone and thyroxine stimulate bone growth Estrogens and androgens stimulate osteoblasts Calcitonin produced in thyroid increases resorption of calcium into bone - released when calcium levels are too high

Bone growth in length

Endochondral ossification also occurs in epiphyseal plates of long bones as they grow in length Cartilage forms first before bone forms Epiphyseal plate - cartilage where bone lengthens from During childhood and adolescence Bone gradually replaced cartilage Due to sex hormones, growth hormone, and thyroid hormone Gradually grow upward and outward The chondrocytes in the bottom layer will gradually be replaced by bone (osteoclasts and osteoblasts) Zone closest to epiphysis (top) is called resting cartilage bc they're just there; anchor epiphyseal plate to bone Zone of proliferating cartilage - slightly larger chondrocytes; undergo interstitial growth; cells actively undergoing mitosis Hypertrophic zone - cartilage cells start to hypertrophy (get excited and big); stop secreting normal matrix and start secreting alkaline phosphate Bone tissue is calcified matrix; osteoblasts build off calcified cartilage; secrete enzymes that pave the wave to turn into bone tissue Zone of Calcified cartilage - chondrocytes are completely dead; perfect breeding ground for osteoblasts to come in and carve that area to build bone tissue Osteoblasts travel upward and gradually replace bottom layer with bone just as cartilage keeps growing outward as well

Aging and bone tissue

From birth through adolescence, more bone is produced than is lost during remodeling In adults, the rates are the same Older individuals, especially post-menopausal women, experience a decrease in bone mass when resorption outpaces deposition

Bone development

Largrst growth at puberty Grow until age of 25 Osteogenesis - umbrella term; bone formation from mesenchymal tissue Ossification - type of osteogenesis; process of replacing other tissues with bone