A & P Chapter 7 : bone tissue

osteoprotegerin

"protects bone" by preventing bone resorption. Osteoprotegerin works as a decoy receptor for RANKL: it binds RANKL and therefore prevents binding to RANK and stimulation of osteoclastogenesis. The ratio of osteoprotegerin:RANKL produced by osteoblasts will determine the extent of bone resorption.

Orthodontic appliances

(braces) reposition teeth Tooth moves because osteoclasts dissolve bone ahead of the tooth, where the pressure on the bone is the greatest -osteblasts

matrix of osseous tissue

1/3 organic and 2/3 inorganic matter

inorganic matter

85% hydroxyapatite ( crystalized calcium phospahte salt) -10% calcium carboate - fluoride, sodium, potassium , magnesium

percentage in Calcium Homeostasis

99% in the skeleton As easily exchangeable calcium ions and more stable hydroxyapatite reserve 18% of adult skeleton exchanged with blood each year

g calcium in adult body (Calcium Homeostasis)

About 1,100

Which of the following mediators reduces bone resorption?

Calcitonin

Calcium homeostasis is regulated by three hormones:

Calcitriol, calcitonin, and parathyroid hormone

Calcium Homeostasis

Calcium and phosphate are used for much more than bone structure Phosphate is a component of DNA, RNA, ATP, phospholipids, and pH buffers Calcium needed in neuron communication, muscle contraction, blood clotting, and exocytosis Minerals are deposited in the skeleton and withdrawn when they are needed for other purposes

solubility product (Mineral Deposition)

Calcium and phosphate ion concentration must reach a critical value called the solubility product for crystal formation to occur

Calcitonin plays a role in bone metabolism by which of the following mechanisms?

Decreasing osteoclast activity by directly binding to receptor on the osteoclast

interstitial growth

bones increase in length -bone elongation is result of cartilage growth within epiphyseal plate - epiphysyse close when cartilage is gone (epiphyseal line)

periosteum

external sheath that covers bone expect where there is articular cartilage -outer fibrous layer -inner osteogenic layer

genereal features ofbone

flat bones long bones short bones irregular bones

What type of connective tissue fiber is found in bone?

type 1 collagen

BONE DISORDERS

yay

Hydrochloric acid ( (mineral resorption)

(pH 4) dissolves bone minerals

PTH raises calcium blood level by four mechanisms

-Binds to receptors on osteoblasts Simulating them to secrete RANKL which raises the osteoclast population -Promotes calcium reabsorption by the kidneys, less lost in urine -Promotes the final step of calcitriol synthesis in the kidneys, enhancing calcium-raising effect of calcitriol =Inhibits collagen synthesis by osteoblasts, inhibiting bone deposition

Types of bone fractures

-nondisplaced -displaced - comminuted - greenstick

intramembranous ossification

1)condensation of mesenchyme into soft sheet permeated with blood capillaries 2) deposition of osteoid tissue by osteoblasts on mesenchymal surfacel entrapment of first osteocytes, formation of periosteum 3) honeycomb of bony trabeculae formed by continued mineral deposition: creation spongy bone 4) surface bone filled in by bone deposition, converting spongy bone to compact bone. Persistence of spongy bone in the middle layer PRODUCES FLAT BONES OF SKULL AND CLAVICLE

Other factors affecting bone

At least 20 or more hormones, vitamins, and growth factors affect osseous tissue Bone growth especially rapid in puberty and adolescence -Surges of growth hormone, estrogen, and testosterone occur and promote ossification -These hormones stimulate multiplication of osteogenic cells, matrix deposition by osteoblasts, and chondrocyte multiplication and hypertrophy in metaphyses

Phosphate Homeostasis numbers

Average adult has 500 to 800 g phosphorus 85% to 90% of phosphate is in the bones Normal plasma concentration is 3.5 to 4.0 mg/dL Occurs in two principal forms HPO42− and H2PO4− (monohydrogen and dihydrogen phosphate ions)

Which of the following is true regarding osteoprotegerin (OPG)?

Binds to and sequesters RANKL

Bone resorption

Bone resorption can be triggered by parathyroid hormone (PTH) in response to hypocalcemia. PTH stimulates the generation of new osteoclasts (osteoclastogenesis). After osteoclasts form, the first step necessary for bone resorption to occur is that the mature osteoclast needs to tightly adhere to the bone, creating a specialized isolated compartment. Once the osteoclast adheres to the bone surface, the membrane adjacent to the bone differentiates as the ruffled membrane. The ruffled membrane contains proteins that acidify the compartment adjacent to the bone. The acid dissolves the minerals in the bone; subsequently, digestive enzymes break down type I collagen and other proteins. Bone resorption ends when the osteoclast dies by apoptosis.

Calcitriol Produced by the following process

Epidermal keratinocytes -Liver -Kidneys

seed crystals (Mineral Deposition)

First few crystals attract more calcium and phosphate from solution

Osteoblast stimulation (in calcitonin)

Increases the number and activity of osteoblasts Deposits calcium into the skeleton

A mature bone remains a metabolically active organ

Involved in its own maintenance of growth and remodeling Exerts a profound influence over the rest of the body by exchanging minerals with tissue fluid

Abnormal calcification (ectopic ossification) (Mineral Deposition and Resorption)

May occur in lungs, brain, eyes, muscles, tendons, or arteries (arteriosclerosis) Calculus

inhibitors (Mineral Deposition)

Most tissues have inhibitors to prevent this so they do not become calcified

Receptor activator of nuclear-factor kappa-B ligand (RANKL) is an important regulator of bone resorption. Which of the following cells is the MAJOR source of RANKL in bone remodelling?

Osteoblasts

Calcitionin lowers calcium concerntraion in two ways

Osteoclast inhibition Osteoblast stimulation

Name the peptide hormone that stimulates osteoclastogenesis.

PTH

Osteoclastogenesis

PTH stimulates bone resorption by osteoclasts, but it does so indirectly. Receptors for PTH are located on osteoblasts, which then signal to bone marrow-derived osteoclast precursors to stimulate their fusion, differentiation and activation. Osteoclast precursors express a cell-surface receptor known as RANK. Osteoblasts express RANKL on the extracellular surface of their plasma membrane.

Which of the following bone modulators primarily utilizes adenylyl cyclase as a mediator for its cellular signaling within osteocytes?

Parathyroid hormone (PTH)

A 55-year-old female with a history of metastatic breast cancer develops shoulder pain without any trauma. Which of the following is involved with the findings shown in Figures A and B?

RANK

RANKL

RANK Ligand)

RANK

RANK stands for Receptor Activator of Nuclear factor-Kappa B

Osteoclast inhibition ( in calcitonin)

Reduces osteoclast activity as much as 70% Less calcium liberated from bones

All of the following substances inhibit osteoclast activity, EXCEPT?

Tumor necrosis factor-alpha (TNF-a)

Calcium homeostasis depends on

a balance between dietary intake, urinary and fecal losses, and exchanges between osseous tissue

Calcitriol

a form of vitamin D produced by the sequential action of the skin, liver, and kidneys

epiphyseal plate

a region of transition from cartilage to bone -functions as growth zone where the bones elongate -consists of typical hyaline cartilage in the middle -metaphysis: zone of transition facing the marrow cavity

kindeys (calcitriol)

add another hydroxyl group, converting that to calcitriol (most active form of vitamin D); also from fortified milk

Liver (calcitriol)

adds a hydroxyl group converting it to calcidiol

Osteocytes

are bone cells. Osteocytes manufacture type I collagen and other substances that make up the bone extracellular matrix. Osteocytes will be found enclosed in bone.

Osteoblasts

are bone-forming cells. They are connective tissue cells found at the surface of bone. They can be stimulated to proliferate and differentiate as osteocytes.

Osteoclasts

are bone-resorbing cells ("-clast" means to break; osteoclasts break down bone). They are large, multinucleate cells that form through the fusion of precursor cells. Unlike osteoblasts, which are related to fibroblasts and other connective tissue cells, osteoclasts are descended from stem cells in the bone marrow that also give rise to monocytes.

epiphyseal plate (growth plate)

area of hyaline cartilage that seperated the marrow spaces of the epiphysis and diaphysis -enables growth in length -epiphyseal line

tendons

attach muscle to bone

Hypocalcemia (Calcium Homeostasis)

blood calcium excess -Vitamin D deficiency -Diarrhea -Thyroid tumors -Underactive parathyroids -Pregnancy and lactation -Accidental removal of parathyroid glands during thyroid surgery

osteoclasts (one type of bone cells)

bone dissolving cells foound on the bone surface via acid phosphatase activity -deveolope from same bone marrow stem cells that give rise to blood cells different origin from rest of bone cells, from moncytemarcophage cell lineage - large cells formed from the fusion of several stem cells ( 3-4 up to 50 nuclei)

inner osteogenic layer (in periosteum)

bone forming cells important to growth of bone and healing of fractures

osteoblasts (one type of bone cells)

bone forming cells (makes osteoid) -lines up as single layer of cells under endosteum and periosteum -nonmitotic -synthesize soft organic matter of matrix which hardens by mineral deposition -stress stimulate cells to multiply -secrete osteocalcin

appositional growth

bone increase in width thorughtout life -depostion of new bone at the surface -osteoblasts on deep side of periosteum deposit osteoid tussue -lay down matrix in layers parallel to surface -forms circumferential lamellae over surface

Osteoclasts are descended from _______. [choose best: fibroblasts, connective tissue progenitors, bone marrow stem cells, monocytes]

bone marrow stem cells

Stress fracture

break caused by abnormal trauma to a bone Falls, athletics, and military combat

Pathological fracture

break in a bone weakened by some other disease Bone cancer or osteoporosis Usually caused by stress that would not break a healthy bone

Calculus (in abnormal calcifcation in mineral deposition)

calcified mass in an otherwise soft organ such as the lung

three main chemical messengers in calcium homeostatis

calcitriol, calcitionin, and parathyroid hormone (PTH)

Calcitriol Synthesis and Action

calcitriol>>>>>>>>>>>>>>>> calcitrioc acid 24-hydroxylase (excreted in urine) ****KNOW THE NAMES OF THIS!!!***

Anabolic steroids

cause growth to stop Epiphyseal plate "closes" prematurely Results in abnormally short adult stature

Fractures

classified by structural characteristics Direction of fracture line Break in the skin Multiple pieces

bone is a composite

combination of two basic structural materials,: -ceramic -polymer

skeletal system

composed of bone, cartilage, and ligaments

bone

connective tissue that conssits of cells, fibers, and ground substance

bone ( osseous tissue)

connective tissue with the matrix harderend by calcium phosphate and other minerals

spongy bone

consists of -silvers of bone called spicules -thin plates of bone call trabeculae -spaces filled with red bone marrow few osteons and no central canals provide strength with minimal weight

spongy (cancellous) bone

covered by more durable compaact bone -skeleton 3/4 compact and 1/4 spongy bone by weight - spong bone in ends of long bones and middle of all other

Mineral deposition (mineralization)

crystallization process in which calcium phosphate and other ions are taken from the blood plasma and deposited in bone tissue OSTEOBLASTS Fibers become encrusted with minerals that harden the matrix --Calcium and phosphate (hydroxyapatite) from blood plasma are deposited along the fibers

diaphysis

cylinder of compact bone to provide leverage

Osteoblasts (Orthodontic appliances )

deposit bone more slowly in the low-pressure zone behind the tooth

irregular bones

elaborate shapes that do not fit into other catergoires SPHENOID, ETHMOID, VERTEBRAE

epiphyses

enlarged ends of a long bone -enlarged to strengthen joint and attach ligament and tendons

Acid phosphatase (mineral resorption)

enzyme digests the collagen

short bones

equal in length and width glide across one another in multiple directions CARPALS, TARSAL

Chloride ions (mineral resorption)

follow by electrical attraction

cartilage

forerunner of most bones -covers many joints surface of mature bones

osteocytes (one type of bone cells)

former osteoblast that have become trapped i matrix where they deposited, AGED. DONE MAKING OSTEOID - lacuna -canacliculi -cytoplasmic processes contributes to homeostatic mechanism of bone density and calcium and phophate ions -when stressed, produce biochemical signals that regulate bone remodling

yellow marrow

found in adults -most red marrow turns into fatty yellow marrow -no longer produces blood

bone marrow

general term for soft tissue that occupies the marrow cavity of a long bone and small spaces amid the trabeculae spongy bone

ligament

hold bones together at the joint

inorganic matrix

hydroxyapatite crystals (Ca3(PO4)2+ Ca(OH)2 -2/3 weight of bone -remaining 1/3 is collagen fibers, calcium salts -cells contribute total of 2% total bone tissue volumn

epiphyseal line

in adults, a bony scar that marks where growth plate used to be

Hydrogen pump (mineral resorption)

in membranes secrete hydrogen into space between the osteoclast and bone surface

Disturbance of calcium homeostasis

in skeleton disrupts function of other organ systems Especially nervous and muscular

Which of the following best describes the mechanism by which osteoprotegerin (OPG) plays a role in RANKL-mediated osteoclast bone resorption?

inhibits RANKL-mediated osteoclast bone resorption by directly binding to RANKL

in human fetus and infant, bone developes by two methods:

intramembranous ossification endochrondral ossification

Normal calcium concentration in blood plasma (Calcium Homeostasis)

is 9.2 to 10.4 mg/dL—45% as Ca2+ can diffuse across capillary walls and affect other tissues; rest in reserve, bound to plasma proteins

Denosumab

is monoclonal antibody that binds to RANKL; thus it mimics the effect of osteoprotegerin. Denosumab (marketed as Prolia®) was approved for the treatment of osteoporosis in June 2010.

articular cartilage

layer of hyaline cartilage that covers joint surface where one bone meets another, allows joint to move freely and friction free

cancaliculi (in osteocytes)

little channels that connect lacunae

long bone

longer than wide, rigid levers acted upon by muscles FEMUR

calcium homeostatis correction for hypercalcemia

look at figure 17.16b

Calcium homeostasis correction fo hypocalcemia

look at the figures 7.16a to know

nutrient foramina

minute holes in the bone surface that allows blood vessels to penetrate

red marrow (myeloid tissue)

nearly in every bone of a child hemopoietic tissue in adults: skull, vertebrae, ribs, sternum, pelvic girdle, and proximal heads of humerus and femur

bone development

ossification or osteogenesis

Name the cell that expresses the signaling molecule RANKL on it surface.

osteoblasts

. Bone cells that are enclosed in bone matrix are called _______.

osteocytes

four principle types of bone cell

osteogenic cells , osteoblasts, osteocytes, osteoclasts

Name the secreted protein that binds RANKL. The osteoporosis drug denosumab works in a similar way.

osteoprotegerin

compact bone

outer shell of long bone

bone resoprtion

performed by active osteoclast stimulated by RANKL in normal process stimulated by PTH in pathologic process (metastatic disease) bone formation

bone formation

performed by inhibiting osteoclasts and stimulating osteoblasts OPG inhibits osteoclasts

resorption bays

pits on surface of bone where osteoclast reside

Osteoblasts (Mineral Deposition and Resorption)

produce collagen fibers that spiral the length of the osteon

hemopoietic tissue (in red marrow)

produces blood cells and is composed of multiple tissues in delicate, ut intricate arrangement that is an organ to itself

flat bones

protect soft organs -curved but wide and thin SKULL, STERNUM

cytoplasmic processes (in osteocytes)

reach into canaliculi

remodeling

result from combined action of the bone dissolving osteoclasts and the bone depositing osteoblasts

Calcitionin

secreted by C cells (clear cells) of the thyroid gland when calcium concentration rises too high

Parathyroid hormone (PTH)—

secreted by the parathyroid glands which adhere to the posterior surface of thyroid gland PTH released with low calcium blood levels

ruffled border

side facing bone surface -several deep infloding of the plasma membrane which increases suface area and resportion effiency

outer fibrous layer (in periosteum)

some outer fibers continuous witht hte tendons that attach muscle to bone -perforating (sharpey fibers): other outer fiber that penerates into bone matrix -strong attachment and continuity from muscle to tendon to bone

medullary cavity ( marrow cavitiy)

space in the diaphysis of a long bone that contain bone marrow

osteogenic (osteoprogenitor) cells

stem cells found in endosteum, periosteum, and in central canals -arise from embryonic mesenchymal cells, multiply continuously to produce new osteoblasts

function of skeleton

support protection movement electrolyte balance acid-base balance blood formation

organic matter

sythesized by osteoblasts -collagen, carbonhydrate-protein complexes such as glycosaminoglycans, proteoglycans, and glycoprotein

mineralization or calcification

the hardening process of bone

Mineral resorption

the process of dissolving bone and releasing minerals into the blood Performed by osteoclasts at the ruffled border -Hydrogen pumps -Chloride ions -Hydrochloric acid -Acid phosphatase

endosteum

thin layer of reticular connective tissue lining marrow cavity -has cells that dissolve osseous tissue and others that deposit it

osteocalcin (in osteoblasts)

thought to be the structural protein of bone - stimulatsinsulin secretion of pancreas -increase insulin sensitivity in adipocytes, limits growth of adipose tissue

lacunae (in osteocytes)

tiny cavities where osteocytes reside

Epidermal kenratinocytes (calicitriol)

use UV radiation to convert a steroid, 7-dehydrocholesterol to previtamin D3