ANS 123 connective tiss

Connective Tissue Terminology

• _____genesis = Cartilage formation

• _____genesis = Bone formation

—

• __________

  • immature, bone anlage cell

• __________

  • mature, cartilage cell

  • produces ECM

—

• __________

  • immature, post‐mitotic, osteoid producing bone cell

• __________

  • Fully‐differentiated __________

  • mature, fixed, bone cell

  • maintain mineral balance of bone

• Chondrogenesis = Cartilage formation

• Osteogenesis = Bone formation

—

• Chondroblast

  • immature, bone anlage cell

• Chondrocyte

  • mature, ECM‐producing cartilage cell

—

• Osteoblast

  • immature, post‐mitotic, osteoid producing bone cell

• Osteocyte

  • Fully‐differentiated osteoblast

  • mature, fixed, bone cell

  • maintain mineral balance of bone

Connective Tissue Terminology

• ________ (immature, post‐mitotic, bone cell)

  • produces osteoid

  • Osteoid = ________ ECM capable of binding Ca2+ Skeleton parts

• ________ (mature, fixed, bone cell)

  • Fully‐differentiated osteoblast

  • maintain ________ of bone

• ________ = Post‐mitotic bone destroying cells

• Osteoblast, Unmineralized

• Osteocyte, mineral balance

• Osteoclasts

Connective Tissue Terminology

• Anlage = embryological groupings of ________ that will form a future structure or organ

  • Ex. Cartilaginous anlage = Cartilage _______ that will become template / model for parts of skeleton

—

• ________ ossification 

  • Bone formation that relies on cartilaginous anlage

• ________ ossification

  • Bone formation that DOES NOT rely on cartilaginous anlage

• stem cells

• Endochondral

• Intramembranous

Connective Tissue Terminology

• Appendicular

  • Bones associated w _________

    • Long bones (of limbs)

    • Fore/hind limbs

    • Pelvic & shoulder girdle

• Axial

  • Everything that is not part of _________

    • Skull, vertebrae,

    • thoracic bones of ribcage

• appendages

• appendicular

Connective tissue

• Provides structure to body

• Supports body

• Most diverse tissue type

  • Function dictates structure

• 3 main categories

  • 1. Proper

    • ex. Dermis

  • 2. Supportive

    • ex. Bone

  • 3. Specialized

    • ex. Adipose

Recipe for Connective Tissue

• Cells (fixed / wandering)

• +

• ECM (protein fibers / ground substance)

Recipe for Connective Tissue

• Cells

  • 1. Fixed 

    • Produce ground substance & proteins that are turned into fibers

    • Specific to each connective tissue type

  • 2. Wandering

    • (blood = only wandering)

• Protein fibers

  • At least one type found in all categories of connective tissue

    • 1. Collagen

    • 2. Reticular

    • 3. Elastic

• Ground substance

  • 1. Chondroitin sulfates

  • 2. Hyaluronic acid

Connective tissue PROTEINS

• _______ collagen

• Collagen _____

• Elas_____

Connective tissue FIBERS

• C______

• R______

• Elas_____

Proteins

• Fibrillar collagen

• Collagen III

• ElasTIN

Fibers

• Collagen

• Reticular

• ElasTIC

PROTEINS — Connective tissue

• _______ = Most abundant protein found in animals (23‐30% of total protein)

---

• Fibrillar collagen

  • Several diff types, but Type ____ = most abundant (skin & muscle)

  • Once secreted by fixed cells, form _______ w other collagen molecs

    • Creates __________

• Collagen III

  • Smaller than _________

  • Does NOT form extensive ________

• Elastin

  • Can be ________ stretched to 2x original length

• Fibrillar collagen

• Type I most abundant

• form cross‐links; tensile strength

—

• fibrillar collagen

• cross‐links

—

• reversibly stretched

FIBERS — Connective tissue

• Collagen

  • Protein = ________

  • Provides ______&______, esp in skin & muscles

• Reticular

  • Protein = ________

  • Support within ______/______/etc., and/or fine ____________

• Elastic

  • Protein = ________

  • Stretchiness

• Fibrillar collagen

• Structure & support

—

• Collagen III

• organs/glands

• fine structural support

—

• Elastin

Cells (review...)

• Fixed: Produce fibers & ground substance

  • Connective tissue proper = Fibroblasts

  • Supportive connective tissue

    • Cartilage = Chondrocytes

    • Bone = Osteocytes

  • Specialized tissue

    • Adipose = Fibroblasts + Adipocytes

• Wandering: Defend & clean

  • All connective tissue = Macrophages & Mast cells

  • Specialized tissue

    • Blood & Lymph = Erythrocytes, Lymphocytes, Platelets

ChondroCYTE

• Fixed _______ cell

• “Immature stage of cartilage cells”

• No cell membrane‐to‐membrane contact bc of _______

  • (pockets in _______ that encapsulate fixed cartilage & bone cells)

• Most abundant during _______

  • Create cartilaginous _______

    • _______ structure in bone formation

    • Made completely of _______

    • Replaced during _______

• When we reach max growth capacity, we lose lots of _______

• Fully mature chondrocytes = present in adults for structures that require _______ support

  • Ex. Joints, trachea, nasal septum

• cartilage

• lacunae, ECM

• development

  • cartilaginous anlage

    • Temporary

    • chondrocytes

    • ossification

• chondrocytes

• mechanical support

Chondrocyte

Chondrogenesis: Overview

• ________ stem / progenitor cells 

  • (origin of ________ lineage) 

  • (progenitor = term indicating multipotency, stem = broader)

• → ______ chondrocytes 

  • Cluster together

• → ______ chondrocytes

  • produce ECM

• Mesenchymal stem / progenitor

  • chondrocyte

• → Prechondrocytes 

• → Mature chondrocytes

Chondrogenesis: Overview

Endochondral ossification (relies on anlage)

Anlage formation

• In order to make anlage, need to go thru ________

• 1. ________ stem cells ⤳ Form uninterrupted _________ 

  • → Commit to ________genesis (________ determination)

    • → ________cytes

• 2. ______chondrocytes → ______chondrocytes

  • Begin to produce components for ______

    • Form uninterrupted ________

      • Condensations take on early bone shape

• 3. Some chondrocytes become future ______ cells ( _______ )

• 4. _________ = Create a gap in template

• 5. _________ = Interzones become joints

  • Delineate future bones

• chondrogenesis

• 1. Mesenchymal, condensations 

  • Chondrogenesis, joint site determination

  • Pre‐chondrocytes

• 2. Pre‐chondrocytes → Mature

  • ECM

  • uninterrupted anlage

• 3. future joint cells ( interzone )

• 4. Cavitation

• 5. Morphogenesis

Endochondral ossification: Anlage formation

Endochondral ossification: Anlage formation

• Anlage = what our bodies use to form long bones

• Fate of anlage pre‐chondrocytes

  • Uninterrupted _________ (pre chondrocytes) → uninterrupted _________ (mature chondrocytes, prod ecm) → _________ formation → _________ divided into bones of skeleton (permanent / temporary)

    • _________ = articular cartilage (fibroblasts)

    • _________ = bone anlage (chondroblasts)

• condensations, anlage, interzone, anlage

  • Permanent = cartilage

  • Temporary = anlage

Endochondral ossification → Anlage →

Temporary anlage chondrocytes

• _______ chondrocytes of temp anlage enter into ______ phase (getting bigger while prolif is occurring) 

• Temporary bc get replaced by bone forming cells

• Prior to birth/hatch, perform double‐duties:

  • Enable anlage to _______ as developing ______ grows

  • Prepare anlage to initiate ________

• mature, hypertrophic

• grow, fetus

• osteogenesis

Prior to birth/hatch, Temporary anlage chondrocytes perform double‐duties:

• Enable anlage to grow as developing fetus grows

  • Produce _______ + Engage in _______ (mature chondcytes), then engage in _______ (______ chondcytes)

    • _______ + Increasing _______ volume = Anlage elongation

• Prepare anlage to initiate osteogenesis

  • Some chondrocytes begin to produce _______ ECM, promoting _______

• ECM

• hyperplasia (mature chondcytes)

• hypertrophy (hypertrophic chondcytes)

• Hypertrophy + Increasing ECM vol = Anlage elongation

—

• mineralized ECM, ossification

Osteogenesis

Long bone anatomy

• _______ = shaft of long bone

• _______ = ends of long bone (distal / proximal)

• _______ = region of bone between epiphyses & diaphysis; important for bone _______

—

• Medullary cavity = hollowed out part of _______

• _______steum = thin connective tissue lining of _______

• _______steum = fibrous connective tissue covering outer surface of bone

  • Plays critical role in bone _________

• Diaphysis = shaft of long bone

• Epiphysis (distal / proximal)

• Metaphysis (bone lengthening)

—

• Medullary cavity = hollowed out part of diaphysis

• Endosteum — medullary cavity

  Periosteum — outer surface (bone‐formation)

Long bone anatomy

Diaphysis , Epiphysis , Metaphysis , Medullary cavity , Endosteum , Periosteum

Osteogenesis

Spongy bone

• Thin, _______ bone tissue

• aka Trabecular / Cancellous bone

  • Temporary

    • Replaced by _______

    • Ex. _______ spongy bone

    • (_____physis)

  • Permanent

    • located in ______/______ of some bones (ex., ____physes of long bones)

    • Network for _______ (_____physis gaps fill w red marrow)

• Thin, porous bone tissue

• compact bone

  • Ex. Woven spongy bone

  • (metaphysis)

• Interior/ends

  • bone marrow

  • (epiphysis)

Spongy bone

Osteogenesis

Compact bone

• Thick, dense bone tissue

• aka Cortical / _______ bone

  • Forms in _____/_____

• Bone tissue that can support _____&_____ attachment (weight bearing)

  

• Cortical / Lamellar

  • rings/layers

• tendon & ligament

Osteogenesis

• ___________ chondrocytes prepare anlage to initiate osteogenesis

  • → Some chondrocytes begin to produce __________, promoting ossification

• Long bone formation

  • Relies on ____________ (___________ ossification)

  • Creates __________ (sites in cart. anlage where cartilage replaced by bone)

    • 1^o ossification center (POC) = Site in _________

    • 2^o ossification centers (SOC) = Sites in _________

• Temporary anlage, mineralized ECM

• cartilaginous anlage (Endochondral ossification)

• ossification centers

  • 1^o = diaphysis

  • 2^o = epiphyses

Ossification centers formation - Long Bone

• 1. ___________ in cartilaginous anlage undergo Hyper_______

• 2. _____________ form around anlage

  • Differentiate into ________ tissue layers

    • => Peri_______ (immature connectiv tiss layer surrndg temp anlage)

• 3. Some chondrocytes in center of diaphysis ___________

  • Initiate Hyper_________

    • Produce ___________

    • Become _______ in ECM (diffusion prevented)

• 4. Peri_______ matures → Peri_______

• 5. ________ forms

  • = Calcifying region of periosteum that encircles _______

• 6. In epiphyses, ________ cells invade cartilage → Cartilage _______

  • Tubes that penetrate embryonic ____physeal cartilage

  • Enable ________ precursors & eventually _________ to penetrate cartilage of epiphyses

• 7. __________ elongates

• 8. In diaphysis, _______ forms

  • Most ECM‐trapped chondrocytes in middle → ________

  • __________ from bone collar invade diaphysis

• 9. In epiphyses, __________ carry endothelial cells (______ precursor cells) from peri_______ → middle

  • _________ form

• 10. ________ form in epiphyses

  • Cartilage canals _______ in center of epiphyses → forms _______ where ossification occurs

• 1. Chondrocytes, Hyperplasia

• 2. Mesenchymal condensations

  • connective tissue, Perichondrium

• 3. stop proliferating

  • hypertrophy

    • mineralized ECM

    • trapped

• 4. Perichondrium matures → Periosteum

• 5. Bone collar

  • diaphysis

• 6. periosteal cells → Cartilage canals

  • epiphyseal

  • blood vessel precursors, blood vessels

• 7. Cartilaginous anlage

• 8. POC forms

  • apoptosis

  • Blood vessels

• 9. cartilage canals, Blood vessel precursor, periosteum → middle

  • Blood vessels form

• 10. SOCs form

  • fuse, cavity

Ossification centers formation

epiphyses = blood vessels invade via cartilage canals

diaphysis = blood vessels invade via bone collar

• When blood vessels invade _______,

  • Blood able to enter

  • Provide _______ & remove _______

  • Final step for _______ maturation

    • = Becomes reservoir for stem cells that differentiate into precursors for _______ cells

  • Carry in

    • Bone _______ cells

    • Bone _______ cells

• anlage

• Provide nourishment & remove waste

• periosteum maturation

  • bone‐forming cell

• Carry in

  • Bone marrow

  • Bone‐forming stem

Ossification centers formation

Blood vessels invade anlage; carry in

• Bone marrow cells

• Bone‐forming stem cells

  • 1st = _________ stem cells

    • Progenitor; renewal (sym/asym divis)

    • Differentiate into Osteo_____

  • 2nd = _________ precursors

    • Progenitor; renewal (sym/asym divis)

    • Differentiate into Osteo_____ → Osteo_____

      • (Osteo_____ can become lining cell or Osteo_____)

• 1. Hematopoietic stem

  • OsteoCLASTS

• 2. Mesenchymal precursors

  • OsteoBLASTS & OsteoCYTE

    • (blasts → lining / cyte)

Chondrocytes & Blood = love‐hate relationship

• Since cartilage is _________, living _________ rely on diffusion from a blood supply for nutrients / waste removal

• Direct contact between _________ & _________ chondro_____ does not end well for the chondrocytes

  • Blood‐bourne morphogens & cells:

    • Terminate _________ in chondrocytes

    • Initiate _________ in chondrocytes

    • Usher in _________ that degrade cartilaginous ECM

    • Replace chondrocytes with _________ & _________

  • (similar to neurons of brain w blood brain barrier)

• avascular, chondrocytes

• blood & anlage chondrocytes

  • hypertrophy

  • apoptosis

  • osteoclasts

  • osteoblasts & osteocytes

Ossification centers formation – 1^o vs 2^o

• 1^o ossification center (Diaphysis)

  • 1. Some chondrocytes stop ________

    • Initiate ________

    • Produce ________ ECM

    • Become trapped in ________

  • 2. Most trapped chondrocytes ________

  • 3. Blood vessels invade from ________

• 2^o ossification center (Epiphyses)

  • 1. Cells from ________ penetrate anlage & create ________

    • Concurrent w initiation of chondrocyte hyper_______

  • 2. Blood vessels invade via ________

POC

• stop proliferating

  • hypertrophy

  • mineralized ECM

  • ECM

• degenerate

• bone collar

SOC

• periosteum, cartilage canals

  • hypertrophy

• cartilage canals

Ossification centers formation – 1^o vs 2^o

• Blood vessels invade from bone collar (1^o) / via cartilage canals (2^o)

  • Support chondrocytes

  • Carry in

    • Bone marrow cells

    • Bone formation stem cells

      • 1. Hematopoietic stem cells → ________

      • 2. Osteo_____ → Osteo_____

• Support chondrocytes

• Carry in

  • Bone marrow cells

  • Bone formation stem cells

    • 1. Hematopoietic stem cells → Osteoclasts

    • 2. Osteoblasts → Osteocytes

Long bone growth

• Simultaneous ________ & ________ ossification

  • Continues post‐natally & terminates around ________

    • Length stops, but diameter continues depending on use

  • Endochondral

    • In ___physes

    • Increase in ________ via growth ________

    • Increase of “dome” of ___physes via spherical growth zone

  • Intramembranous

    • In ___physis

    • Increase in ________ via ________ growth (Modeling)

• endochondral & intramembranous; sexual maturity

• Endo:

  • Epiphyses

  • Length

  • via Growth plate

• Intra:

  • Diaphysis

  • Diameter

  • via Appositional growth

What happens inside 2^o ossification center?

• SOCs (in ___physes)

  • ___physis become filled w _______ bone, except for region of cartilage in metaphysis (______________)

  • Chondrocytes in _______ continue ossification process (_______ing)

    • Each one progresses thru diff functions w time

      • Roughly fall into _______ based on activity of chondrocytes

    • Allows for _______ growth (growth in the in‐between space; btwn epiphysis / diaphysis)

• epiphyses

• Epiphyses, spongy, Epiphyseal/Growth plate

• growth plate, lengthening

  • layers

  • interstitial

Growth (epiphyseal) plate layers/zones

(from epiphyseal side)

• 1. _________ 

  • (infrequent mitosis)

• 2. _________

  • (= Hyperplasic)

• 3. _________

• 4. C_________/_________

• 5. _________

• Resting 

• Proliferating 

• Hypertrophic

• Calcification/Apoptotic

• Ossification zone

Growth (epiphyseal) plate layers/zones (from epiphyseal side) – (chondrocyte activity in ea layer)

• 1. Resting (infrequent mitosis)

  • Produce _________

  • Function(s) uncertain

    • Anchor grwth plate in SOC?

    • Source of chondblast stem cells?

    • Prevent prolif chondcyts from terminal diffntn?

• 2. Proliferating (= Hyperplasic)

  • Frequent _________ / cell _________

    • ability bc still close to blood supply providng nourishment

  • Produce _________

  • Organize into _________

• 3. Hypertrophic

  • Enter _________ differentiation (truly mature chondcytes)

  • Produce _________ cartilage _________

• 4. Calcification/Apoptotic

  • Close proximity to blood vessels likely terminates _________ & triggers _________

• 5. Ossification zone

  • Changeover from m_________ c_________ ECM → o_________ c_________ ECM of bone-forming cells

• Produce ECM

—

• mitosis / cell division

• Produce ECM

• Organize into columns

—

• terminal differentiation

• Prod mineralized cartilage ECM

—

• terminates hypertrophy, triggers apoptosis

—

• mineralized cartilaginous → ossified calcified

Ossification zone/front

• Region of true bone _________

  • upper growth plate regions = _________ ECM, ossification zone = _________ bone ECM

  • _________ cells from _____physis blood vessels invade via cartilage canals

    • Help terminate chondrocyte _________ & trigger _________

    • Makes room for _________ cells

• bone elongation

  • cartilaginous, ossified bone

  • Endothelial cells, metaphysis

    • hypertrophy, apoptosis

    • bone‐forming cells

Bone-forming cells:

• From hematopoietic stem cells (of ___physis / _______ cavity)

  • Osteo_____

    • Multi‐nucleate, macrophage‐like cells

• From mesenchymal precursor cells (of per______)

  • Osteo_____ cell

    • Multipotent bone stem cell

  • Osteo_____

    • Immature, post‐mitotic, osteoid creating cell

  • Osteo_____

    • Fully‐differentiated / mature osteoblast

• diaphysis / medullary cavity

  • Osteoclast

• periosteum

  • Osteogenic cell

  • Osteoblast

  • Osteocyte

Bone-forming cells:

• From hematopoietic stem cells (of diaphysis / medullary cavity)

  • OsteoCLAST

    • Multi_____, ______‐like cells

    • ________ ECM, especially bone (clast = destroy)

      • Destruction in adults almost exclusively calcified bone, but growth plate has period where destroyed ECM is cartilaginous origin

• From mesenchymal precursor cells (of periosteum)

  • Osteogenic cell

    • Multi_____ bone stem cell

    • Produce osteo______ & ________ cells

      • via symmetric/asym divis

      • (________ cells = dormant osteoblast precursors)

    • Stored in ________

  • OsteoBLAST

    • Immature, post‐mitotic, ________ creating cell

    • Forms bone _______ (______ = special ECM)

  • OsteoCYTE

    • Fully‐differentiated / mature ________

      • osteo______ gets trapped in _______ → maturation into osteocyte

    • “Trapped” in ________ of _______ bone matrix

    • Maintain _________ of bone

• Multi‐nucleate, macrophage‐like

• Resorb ECM

—

• Multipotent

• osteoblasts & bone‐lining cells

  • Bone‐lining cells

• periosteum

—

• osteoid

• bone matrix (osteoid = special ECM)

—

• osteoblast

  • osteoblast, osteoid

• lacunae, calcified

• mineral balance

Ossification zone/front

• Region of true bone elongation

  • Arrival of bone forming precursor cells via blood vessel of cartilage canals

    • (Circulatory syst traveling from middle of diaphysis → metaphysis; carries osteoclasts both drxns to metaphyses)

    • 1. Osteo______ PRECURSORS mature → Osteo______

      • → _______ cartilage ECM

      • Attach to calcified/mineralized ECM & resorb mineralized ECM to make room for osteo______

    • 2. Osteo______ PROGENITORS mature → Osteo______

      • → deposit ________ (fill in space created by osteo_____)

      • _______ = UNmineralized bone ECM

  • Proliferating _______ chondrocytes push epiphysis further away from diaphysis → bone lengthens 

  • _______ cells trail chondrocytes → deposit bone

    • (cytes replaced by ossified bone tiss)

• 1. Osteoclast precursors → Osteoclasts

  • dissolve cartilage ECM

  • make room for osteoblasts

• 2. Osteoblast progenitors → Osteoblasts

  • deposit osteoid, osteoclasts

  • Osteoid

• growth plate, lengthens 

• Bone forming cells

Lengthening termination

• Lengthening continues while chondrocyte _________ in growth plate outpaces bone _________

  • Androgens = puberty spurts; after puberty, stabilize

• Once _________ catch up to chondrocytes in proliferation zone, growth plate ______/______

  • Epiphyseal closure = ____physes fuses to ____physis

  • Becomes epiphyseal line after closure

• chondrocyte proliferation > bone formation

• osteoclasts, ossifies / fuses

  • epiphyses fuses to diaphysis

1^o ossification center

• POC (in ___physis)

  • Arrival of bone forming cells via blood vessels of _______

  • 1. Osteo____ precursors mature → _______ cartilage ECM

    • Make room for osteo______

  • 2. Osteo______ produce ______

  • 3. _______ surrounds some osteoblasts

    • Trapped osteoblasts → become _______

  • 4. T________ matrix of osteoid forms

    • (woven spongey bone, Fills entire ____physis)

  • 5. Blood vessels invade

    • become crowded & condense into _________ marrow

  • 6. Osteoblasts from _______ begin to produce ________ bone

• Along the way, _________ cavity forms

• diaphysis

  • periosteum

  • 1. Osteoclast precursors mature & resorb cartilage ECM

    • Make room for osteoblasts

  • 2. Osteoblasts produce osteoid

  • 3. Osteoid surrounds some osteoblasts

    • Trapped osteoblasts → become osteocytes

  • 4. Trabecular matrix of osteoid forms

    • Fill entire diaphysis

  • 5. Blood vessels invade

    • Blood vessels become crowded and condense into red marrow 

  • 6. Osteoblasts from periosteum begin to produce compact bone

• Along the way, Medullary cavity forms

1^o ossification center (POC, diaphysis)

• Along the way, Medullary cavity forms

  • ________ in POC activated

    • Resorb _______ _______ bone from center‐outwards → creates Medullary cavity

      • (bone tiss in diaphysis destroyed to create boneless cavity)

  • ________ added to outside of diaphysis walls as medullary cavity forms

    • = ________ growth via __________ ossification

      • Growth that is “next to” or “side‐by‐side” (sideways expansion)

      • Creates ______/_______ bone (as opposed to spongey)

    • (appositional growth = growth one side, destruction other side)

• Osteoclasts

  • woven spongy bone

• Bone

  • Appositional, intramembranous ossification

    • lamellar, compact bone

1^o ossification center

• Modeling via appositional growth

  • 1. ________ from periosteum produce _______

  • 2. _______ “seeps” under _______ & forms bone

  • 3. Osteoid _______

  • 4. Entombs osteo_____ ↠ Osteo______

  • 5. __________ cells proliferate

    • (Some become next round of osteoblasts)

  • 6. Osteo_______ in ________ resorb bone

    • Without this, bones would become too thick & heavy

• Osteoblasts, osteoid

• Osteoid, periosteum

• Osteoid calcifies

• Osteoblasts ↠ Osteocytes

• Bone‐lining cells

• Osteoclasts, medullary cavity

1^o ossification center

• Modeling via appositional growth

  • Creates ________, ________ bone

    • _______ allow blood supply to osteocytes

  • Unit is the _______ (aka Haversian system)

    • Column of _______ bone that runs the length of _____physis

    • Formed from concentric ______ of compact bone ______

    • Surrounds blood vessel (has arteries + veins)

• lamellar compact

  • Lamellae

• Osteon

  • compact, diaphysis

  • lamellae, ECM

Long bone growth

• Epiphysis (SOC)

  • enlarges by growth of _______ & replacement by _______

  • _________ occurs via _________ ossification

• Shaft (diaphysis) 

  • elongates bc _________ grows in growth plate & is replaced by _______ in _______ (diaphysis)

  • Width via ________ / ________ ossifictn

• Yellow marrow:

  • Comprised mostly of _______ tissue

  • ________ canal in ____physis

• Red marrow:

  • Chief _________ forming tissue in adults

  • Upper region near ____physis

• Epiphysis ,

  • cartilage , bone

  • Lengthening = endochondral

• cartilage , bone in POC (diaphysis) 

• appositional growth / intramemb ossifictn

• —

  • adipose tissue

  • Medullary canal in diaphysis

• —

  • blood cell forming tissue

  • epiphysis

Timing of growth termination depends on:

• G________

• N________

• ________ changes 

  • (often assoc w sexual maturity; Hormone changes)

  • Ex horses; removal of the testicles before the animals have hit puberty can cause a delayed closure of the growth plate; castrated geldings will actually grow taller than stallions who remain intact

• ________ factors

  • Compressional force inhibits growth → Earlier termination

• Genetics

• Nutrition

• Metabolic changes 

• Mechanical factors

Bone remodeling: an overview

• Occurs _________

• Adapt to changing circumstances

• Purposes:

  • 1) _______ calcium

    • (calcium homeostasis, allow appropriate lvls of calcium)

  • 2) Replace _______ tissue

  • 3) Adapt to _______

  • 4) Repair _______

    • Increased fracture risk

    • Worsens w age

• throughout life

• Adapt to changing circumstances

—

• a) Mobilize calcium

• b) Replace bone tissue

• c) Adapt to stress

• d) Repair damage

Remodeling steps

• 1) Re_______ (osteoclasts)

• 2) Re_______ (apoptosis)

• 3) F_______ (osteoid)

• 4) Re_______ (bone lining cells)

• 1) Resorption

• 2) Reversal

• 3) Formation

• 4) Resting

Remodeling

• Spongy bone

  • 1) Resorption

    • Osteoclasts recruited to create _______ ____/____

  • 2) Reversal

    • ________ undergo ________

  • 3) Formation

    • ________ produce ________

    • Some ________ get trapped in ________

  • 4) Resting

    • Osteo______ → osteo______

    • New __________ cells

• Compact bone

  • 1) Resorption

    • Osteoclasts recruited to create __________

      • (tunnel allowing osteoclasts to resorbs damaged bone)

  • 2) Reversal

    • Osteo____ undergo ________

    • Osteo____ attracted to ________

  • 3) Formation

    • ________ produce ________ w/in cone in ________ pattern

    • Some ________ get trapped in ________

  • 4) Resting

    • New __________ cells

1. resorption pit/cavity

2. Osteoclasts , apoptosis

3. Osteoblasts , osteoid | osteoblasts , osteoid

4. Osteoblasts → osteocytes | new bone lining cells

— — — — — — — — —

1. cutting cone

2. Osteoclasts , apoptosis | Osteoblasts , cutting cone

3. Osteoblasts , osteoid , concentric pattern | osteoblasts , osteoid

4. New bone lining cells

Age related changes in homeostasis

• Bone homeostasis “balance” becomes ________

  • Bone r________ by osteo______ does not keep up w r________ by osteo______

• Decreases _______ integrity of skeleton

  • Esp when worsened w disease (eg estrogen deficiency)

• ________ lose ability to produce as much osteoid

  • Central canal of osteons become ________

    • → Increased bone ________

  • ________ from neighboring osteons become so large that osteons fuse = ________

• negative

  • replacement by osteoblasts < resorption by osteoclasts

• mechanical integrity

• Osteoblasts

  • bigger, bone porosity

  • Central canals, Osteoporosis

Mature anlage chondrocytes:

• Temporary chondrocytes

  • Within __________

• Permanent chondrocytes

  • Ends of the gaps

  • Produce __________ in synovial joints

  • Synovial joints:

    • 1. _______ cartilage

    • 2. Synovial _______

      • Synovial _______ (lubrication)

    • (articular cartilage + synovial membrane allow for _______ mvmnt)

    • 3. _______ joint capsule/membrane

    • 4. Bone

• bone anlage

—

• articular cartilage

• 1. Articular cartilage

• 2. Synovial membrane

  • Synovial fluid (lubrication)

• (frictionless mvmnt)

• 3. Fibrous joint capsule/membrane

• 4. Bone

Articular cartilage (permanent chondrocytes)

• Sheet of _______ cartilage at ends of bones forming joint

• Reduces _______ between bone ends & absorbs _______ pressure

• Main components = _______

  • Produce _______ (collagen + proteoglycans + water)

• No _______ — relies on diffusion of nutrition from / wastes into _______

• Uncalcified vs Calcified regions

  • _______ region separated into zones based on:

    • 1. Shape & direction of _______

    • 2. Direction of _______

  • Zone _____ = adjacent to synovial joint cavity

  • _______ region is deepest (closest to bone)

Articular cartilage growth

• Zone 1

  • Proliferative chondrocytes enable cartilage to _______ / grow _______

• Zone 3

  • Proliferative chondrocytes enable cartilage to _______

• hyaline

• friction, compression

• chondrocytes

  • ECM (collagen + proteoglycans + water)

• No vascular system, synovial fluid

• Uncalcified

  • chondrocytes

  • fibers

• Zone 1

• Calcified

—

• 1 = lengthen / grow laterally

• 3 = get thicker

Adipose tissue terminology

• Adipoblast = Adipocyte precursor

• Adipocyte = Mature, fixed cell of adipose tissue

  • _______ lipids

• Lipogenesis

  • Lipid (triglyceride) formation from _________

• Lipolysis

  • Lipid (triglyceride) deconstruction → _________

• __________ = small lipid droplets assoc w pre-adipocytes

• __________ = large lipid bubble assoc w adipocytes

• __________ = Transiently amplifying, fixed cell of adipose tissue

• stores lipids

• fatty acids

• fatty acids

• Multi-locular lipid

• Uni-locular lipid

• Pre-adipocyte

Adipose tissue

• Adipocytes (specialized cells)

  • Mostly ________ in the form of fat (triglycerides)

  • very little __________

• Facts about fat

  • Modified ________ tissue

    • No true ________

• Functions:

  1. ________ storage & mobilization 

     • → Adipose tissue _________

       • Switching between _______&_______

     • More energy contained in 1 unit of fat than carbs / proteins

  2. ________ (blubber)

  3. ________ (padding)

  4. __________ (e.g., brown fat)

• storage

• ground substance

• connective, ECM

—

• Energy

  • metabolism

  • lipogenesis & lipolysis

• Insulation

• Protection

• Generating heat

Adipose tissue

• Significant ________

• From ________ perspective, fat can be problematic

  • Both desirable & also a waste product for producers

    • Small amounts in the proper location desired by consumers

    • Large amounts in the wrong location are rejected by consumers

• Composition of adipose tissue

  • Lipids = ________ = 76-95%

  • ________ = 5-20%

  • Some ________ = 1-4%

• species diffs

• production

• Lipids = Triglycerides = 76-95%

• H2O = 5-20%

• Some proteins = 1-4%

Adipogenesis

• 1. Mesenchymal ________ cells ⤳ Adipoblast

• 2. Surrounding connective tissue is _________

  • = Stroma (necessary for transport of FAs & TGs)

• 3. ________ form clusters = _________

  • undergo Hyper______

• 4. ______locular lipids form

  • Adipoblasts ↠ _______cytes

• 5. _______cytes undergo differentiation

• 6. ______locular lipids ↠ ______locular lipid

  • _______cyte ↠ _______cyte

  • As lipids form, nucleus gets pushed aside & lobules become _______

• 1. Neural crest cells

• 2. Vascularized = Stroma

• 3. Adipoblasts 

  • Lobules → Hyperplasia

• 4. Multi-locular lipids

  • Adipoblasts ↠ Pre-adipocytes

• 5. Pre-adipocytes

• 6. Mutilocular lipids ↠ Uniloclular lipid

  • Pre-adipocyte ↠ Adipocyte

  • Lobe

Adipogenesis

• Majority of new adipocytes form ________ birth/hatch with _________ hyperplasia occurring at slower rate throughout life

• Species diffs in timing of slowdown for post-natal adipogenesis

  • Cattle: ~birth

  • Sheep = by 2-3 wks

  • Chickens = by 15 wks

  • Pigs = by 7 months

Adipose tissue growth

• Occurs mostly through _________ throughout life

  • = Main mechanism for adipose tissue growth

• but __________ will occur in adults if subjected to conditions that cause clinical obesity

• prior to birth/hatch, post-natal

• hypertrophy

• hyperplasia

Adipose tissue growth

• Adipose tissue _________ = Lipogenesis

  • __________ → Triglyceride _________ in adipocytes

    • Depending on devel stage, TGs form into _________ or _________ droplets

  • Lipogenesis

    • 1. Synthesis: Creation of ________ chains

    • 2. Esterification: Sticking 3 ______ chains onto ________ backbone

  • TGs:

    • too big to pass between endothelium of blood vessel walls to leave circulatory system & entire adipocytes

    • Once they reach adipose tissue via circulatory system, they need undergo __________ to pass out of circulatory system & cross adipocyte membrane

• hypertrophy

• accumulation, multilocular or unilocular

• fatty acid (FA), FA , glycerol

• lipolysis