Bones and Cartilage, Second Edition: Developmental and Evolutionary Skeletal Biology

865 Pages·2015·155.176 MB·English

by  Brian K. Hall

Bones and Cartilage
Bones and Cartilage
Developmental and Evolutionary Skeletal Biology
Second Edition
Brian K. Hall
Department of Biology, Dalhousie University, Halifax, NS, Canada
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Preface
The first few paragraphs and bullet list are taken pretty extinct taxa. Veterinarians, physical anthropologists, radio-
much verbatim from the Preface to Developmental and graphers,forensicscientists...thelistgoeson.
Cellular Skeletal Biology (Hall, 1978a in references). Bones come in all shapes and sizes. There are long
Their durability attests to the wide number of disciplines bones,flatbones,curvedbones,bonesofirregularandgeo-
forwhichtheskeletonwasandremainscentral. metrically indefinable shapes, large and small bones.Bones
The skeleton has fascinated humankind ever since it exhibitbumps,ridges,grooves,holesanddepressionswhere
was realised that, aside from one or several sets of genes, theyarticulatewithotherbonesorattachtotendonsandliga-
bare bones are our only bequest to posterity. The skeleton ments, and where nerves and blood vessels course through
is more than an articulated set of bones, however. In them. Some bones and cartilages arise within the skeleton
humanskeletons,thefollowingholdtrue: andareintegralpartsofit.Othersariseoutsidetheskeleton,
some as sesamoids or ossifications within tendons or liga-
(cid:1) three-dimensional conformation establishes the basis
ments,othersaspathologicalossificationsinwhatotherwise
ofourphysicalappearance;
wouldbesofttissues.Bonesandcartilagesmaydevelopdur-
(cid:1) formation and rate of differentiation determine our
ingembryonicorfetallife,inlarvalstagesorinadulthood(cid:1)
shapeandsizeatbirth;
often late in adulthood (cid:1) during normal ontogeny, wound
(cid:1) postnatal growth orders us among our contemporaries
repairorregeneration.Bonesmodifythemselvesinresponse
andsetsourfinalstature;whileits
to injury, disease or parasitic infection, in the aftermath of
(cid:1) decline in later life is among the primary causes of
surgery, as a defensive response to predators, as a conse-
lossoftheswiftnessandagilityofyouth.
quence of domestication or hibernation and through evolu-
Notsurprisingly,theskeletonisacentralfocusofmany tionaryadaptations.
scientificandbiomedicaldisciplinesandinvestigations. The previous edition of this book was published in
For developmental or cell biologists, the skeleton 2005. It and this second edition are concerned with the
provides an ideal model for studies of gene action in nature of bones and cartilages and the cells that make
normal and abnormal development, cell differentiation, them: how skeletal cells, tissues and organs are made,
morphogenesis, polarised growth, epithelial(cid:1)mesenchymal develop and age, and how they evolved. In the preface to
interactions, programmed cell death and the role of the the first edition I set out some 20 questions concerning
extracellular matrix. The skeleton supplies geneticists with skeletaldevelopmentand11questionsconcerningskeletal
a permanent record of the vicissitudes of its growth, evolutionA. I will not list those questions again. Many
wherebythephenotypicexpressionofgeneticabnormalities have been answered in the intervening 10 years (the
canbestudied.Orthopaedicsurgeonsearnalivelihoodfrom literature for the first edition went into 2004), but many
correcting abnormalities and breaks, while orthodontists have not. The aim in this as in the previous edition is to
andoralsurgeonsusetheirknowledgeofboneresorptionto analyse and evaluate studies of the development, growth
correct the position of teeth displaced consequent to alveo- and evolution of the skeleton and of skeletal tissues to
lar bone dysfunction. Physiologists, biochemists and nutri- provide a synthesis of the field of Developmental and
tionists are concerned with the skeleton’s store of calcium EvolutionarySkeletalBiology.
andphosphorusanditsresponsetovitaminsandhormones,
while haematologists find that the skeleton houses the pro-
genitorsofthebloodcells.Pathologistsendeavourtounder-
stand the disease states that result from abnormalities in
A. I was stimulated to prepare this list by the Agenda of 45 questions
skeletal cellular differentiation or function; surgeons want
used by Gavin de Beer to conclude his Development of the Vertebrate
to prevent formation of skeletal tissues in the wounds that
Skull (de Beer, 1937, pp. 512(cid:1)515). I answered several of de Beer’s
bear witness to their work. Vertebrate palaeontologists
questionsinmyownPh.D.researchandhopedasimilarlistwouldstim-
make their living from the analysis of the skeletons of
ulateotherskeletalbiologiststodothesame.
xv
xvi Preface
ORGANISATIONAL CHANGES segmentation. In tetrapods, vertebral development is initi-
ated by chondrogenesis of sclerotomal cells, and segmen-
I have kept the same organisation in this edition as in the
tation is a function of the sclerotomal mesenchyme. One
first. Every chapter has been revised and updated exten-
consequence is that relationships among notochord, chon-
sively and the single chapter in Part XV (Evolutionary
droid and cartilage have been reevaluated in the context
Skeletal Biology) is now two (44 and 45) devoted to the
ofwhethernotochordisaformofcartilage.
origin of skeletal variation and organismal variability in
The evolutionary origins of cartilage have been rein-
producing changes to the skeleton. Because the flow is the
terpreted on the basis of new phylogenetic, cellular and
same, I will not provide a detailed outline of the organisa-
genetic data, including the importance of gene regulatory
tionofthebookhere.Rather,I(a)haveaddedintroductions
networksinchondrogenesis(andosteogenesis).
toeachofthe15partsthatoutlinethetopicsofthechapters
Dedifferentiation of osteoblasts has been identified as
ineachofthoseparts,and(b)summarisebelow(andonthe
the source of blastemal cells in regeneration of fin rays in
backcover)someofthemajoradvancesinunderstanding.
zebrafish.
The literature from 2004 to around August 2014 has
Recent data on a mesodermal rather than neural crest
been analysed and integrated into the book. In doing so I
origin of teleost fin rays and scales are analysed. One of
have reduced the number of references by 8% to 6,182. I
many consequences is a reevaluation of the proposal by
was able to do this by including only key references to
Smith and Hall (1993) of the recognition of the exoskele-
older studies by individuals or from individual laborato-
ton and the endoskeleton on the basis of their origin in
ries, marking those with an asterisk in both the reference
neural crest or mesoderm, respectively. The division into
listandinthetext.Formorecompletelistsofearlierstud-
exo- and endo- remains valid, but not on the basis of
ies, refer to the first edition. Major reviews also are iden-
germlayeroforigin.
tified with an asterisk. Additionally, and for ease of
There is increased discussion of dinosaur bone based
working from the reference list, I have added the chapter
on palaeohistology and evaluation of whether skeletal
(s)inwhichaparticularreferenceiscitedinsquarebrack-
growthiseverindeterminate.
ets at the end of the citation in the reference list. A ran-
Discovery of ‘avian’ secondary cartilage in dinosaurs
domexampleis:*Anderson,H.C.(1985).Matrixvesicle
is discussed in relation to dinosaur origins of birds and
calcification: Review and update. In Bone and Mineral
theevolutionofsecondarychondrogenesis.
Research/3 (W. A. Peck, ed.), pp. 109(cid:1)149. Elsevier
There has been expanded treatment of stem cells in
SciencePublishersB.V.,Amsterdam.[22].
embryos and adults, including mesenchymal stem cells
Most figures from the first edition have been retained
and their use in genetic engineering of cartilage, and the
and 45 new figures have been added. Major terms and
conceptofthestemcellniche.
concepts are placed in bold or in italics in the text. As in
There is enhanced discussion of resolution to hurdles
the first edition, references, comments and elaborations
associated with in vitro culture of articular cartilage and
(and a few asides) are in endnotes at the end of each
repairinvivo.
chapter. A detailed single subject and taxonomic index is
Since 1968 my research has been supported continu-
provided. Acknowledgements to individuals who gener-
ously by the National Research Council (NRC) and then
ously commented on sections of text are included as end-
the Natural Sciences and Engineering Research Council
notesintheappropriatechapters.
(NSERC) of Canada (grants A5056 and 257447-02). I
have also had additional support, from time to time, from
CONCEPTUAL CHANGES the Research Development Fund and Killam Trust of
Dalhousie University and from funds associated with the
The back cover contains a list of some of the changes in George S. Campbell Chair in Biology, a University
content from the first edition. Here I highlight some of the Research Professorship, the Victoria General Hospital
substantive changes in our understanding of skeletal devel- (Halifax), the Medical Research Council (Canada), the
opmentandevolutionfromresearchoverthepastdecade. Canadian Institutes of Health Research, the Killam Trust
We now have an appreciation of the integrated and of the Canada Council for the Arts, and the US National
coordinated functioning of the vascular, haematopoietic InstitutesofHealth(NIH;grant45344).Toalltheseagen-
andskeletalsystemsinwholeorganismphysiology. cies, my heartfelt thanks. I am enormously grateful to Pat
Although known since Thomas Huxley’s time Gonzalez, Karen East and Kirsty Halterman of Academic
(Huxley,1859),ourunderstanding ofthefundamental dif- Press/Elsevier for the care and professionalism with
ferences in vertebral development between teleost fish which they spearheaded the project and the manuscript
andtetrapodshasbeenexpandedgreatly.Infish,vertebral throughdevelopmentandproduction.
developmentisinitiatedbymineralisationofthesheath of
the notochord, which also is responsible for vertebral BrianK.Hall
Epigraphs
Problems of the developmental physiology of bone have always had a great fascination for those who have studied
them. That fascination is likewise easily understood when we reflect how notable an example is provided by bone
ofthewayinwhich, fromtheapparentlysimple, morecomplexproblemsarise,andhowthepursuitofthesefurther
problemsleadstheinvestigator,if[s]hebesominded,straighttofundamentalproblemsofthenatureoflifeitself.
J.C.Brash,1934,Someproblemsinthegrowthanddevelopmentalmechanicsofbone.
Edin.Med.J.41,p.306
This type of research [morphological work] is laborious and requires specialized training, especially in the dissec-
tion and identification of minute nubbins of developing cartilage and bone that are usually overlooked by reason-
ablepeople.
J.M.Leisetal.,1997.proceedingsofthesymposium‘FishLarvaeandSystematics:
OntogenyandRelationships.’TheInternationalLarvalFishConference,June16(cid:1)30,1995heldinSydney
Australia.Bull.MarineSci.60,1(cid:1)212
When my books are published, I keep to myself. I write every day of the week — otherwise I’m silent. I am tempted
by the thought of not publishing at all — isn’t the work all I need, the work and the working? What does it matter
anylongerifI’mincontinentandimpotent?
PhilipRoth,2007.ExitGhost.JonathanCape,London.p.5
xvii
Part I
Vertebrate Skeletal Tissues
WhenTessmademetooweepy,Iturnedtothetimelessserenityofthefrontalbones.
A.d’A.Bellairs,1989.TheIsleofSeaLizards.p.93.
DurrellInstituteofConservationandEcology,UniversityofKent,Canterbury.
The importance for the classification of life of the fundamental differences between skeletal tissues
was recognised by Aristotle (384(cid:1)322 BC), who separated the cartilaginous fishes (Chondrichthyes)
from the bony fishes (Osteichthyes) on the basis of the presence of a cartilage- or a bone-based
endoskeleton, respectively. The four classes recognised by Linnaeus (Mammalia, Aves, Amphibia,
Pisces) were recognised as representing a single group of animals with bone by J. G. C. Barsch,
who, in 1788, named them Knochenthiere and Ossea. Renamed by Jean-Baptist Lamarck in 1801
as animaux a` vertebres, we now know them as Vertebrates, the name given to them by Ernst
Haeckelin1866(Nielsen,2012).
Bone and cartilage are two of four vertebral skeletal tissues. The other two are dentine and
enamel. This may seem an unlikely list. Normally, we think of cartilage and bone as skeletal tissues
and of enamel and dentine as dental tissues associated with teeth. Enamel and dentine, however,
arose evolutionarily as skeletal tissues in the exoskeletons of early jawless and toothless vertebrates.
These four tissues are distinguished by the nature of their cells and by the nature of the extracellular
matrices produced by thosecells. Osteoblasts and osteocytes are bone-forming cells. Chondroblasts,
chondrocytes and hypertrophic chondrocytes are cartilage-forming cells. Odontoblasts synthesise
anddepositdentinematrix.Ameloblastssynthesiseanddepositenamelmatrix.
Chapter 1 introduces the four skeletal tissues and the four cell types, traces their origins to the
outset of vertebrate evolution 450 million years ago, examines the concept of vertebrate endo- and
exoskeletons and introduces four tissues (cid:1) cementum, enameloid, chondroid, chondroid bone (cid:1)
thatareintermediatebetweenboneandcartilage,boneanddentineanddentineandenamel.
Chapter 2 is devoted to bone as a skeletal tissue, including discovery of the basic structure of
bone, distinctions between cellular and acellular bone, the features and gene products of
osteocytes and the processes of intramembranous and endochondral ossification. Growth,
modelling, remodelling and ageing of bone are discussed, as is the significance of the presence of
boneinsharksandrays.
Chapter 3 is devoted to the three types of vertebrate cartilages (hyaline, elastic, fibrous),
chondrones as fundamental structural units of cartilage, how cartilage grows, cartilage in sharks
andraysandthespecialisedcartilageandproteinsfoundinlampreysandhagfish.
Chapter 1
Vertebrate Skeletal Tissues
In the pioneering stages of Natural Science we recognize the work of collecting, describing and classifying the typical units as a
fundamentalnecessity.Thestudyoftheirmorphologyandtheirhistorybelongstoamoreadvancedperiod.
J.M.Petrie,1914,HandbookforNewSouthWales,BritishAssociationforthe
AdvancementofScience,Sydney,Australia,citedfromL.Gilbert,1997,p.283.
Historically, the distinction between cartilage and bone has with teeth and with dermal scales in fishes (see Box 2.4).
been recognised since at least the time of Aristotle Enamelanddentine,however,aroseevolutionarilyasskele-
(384(cid:1)322 BC), who recognised and separated the cartilagi- tal tissues in the exoskeleton (dermal, dermo-skeleton) of
nous fishes (Chondrichthyes) from the bony fishes early jawless and toothless vertebrates (Figure 1.1,
(Osteichthyes)bythepresenceofeitheracartilaginousoran Table 1.1). Bone also is a primitive tissue of that exoskele-
osseous skeleton. Two thousand fifty years later, the oldest ton,providinganattachmenttissueforelements(odontodes)
articulated chondrichthyan, the 50- to 75-cm-long composedofdentineandenamel.
Doliodus problematicus, was described from the Early At the cell/tissue level, these four tissues are distin-
Devonian (409 million years ago [mya]) of New guishedbythenatureoftheircellsandbythenatureofthe
Brunswick, Canada. Previously known only from iso- extracellularmatricesproducedbythosecells(seeChapters
lateddermalscalesandteeth,thisspecimenincludesthe 2(cid:1)4).Terminologyforskeletalcellsisasfollows:
braincase, prismatic mineralised cartilage and paired
(cid:1) Osteoblastsandosteocytesarebone-formingcells.
spines associated with the pectoral fins, previously
(cid:1) Chondroblasts, chondrocytes and hypertrophic
unknown as a feature of cartilaginous fishes (R. F.
chondrocytesarecartilage-formingcells.
Miller et al., 2003; Turner and Miller, 2005; and see
(cid:1) Odontoblastssynthesiseanddepositdentinematrix.
Chapter3).
(cid:1) Ameloblastssynthesiseanddepositenamelmatrix.A
Skeletaltissuesareevenmoreancient,withoriginsreach-
ing back perhaps three-quarters of a billion years. Cartilageformsthebasisofthesecondvertebrateskel-
Nevertheless, the number of skeletal tissues or organs is etal system, which is the endoskeleton (Table 1.1), which
limited. Thomas et al. (2000) evaluated 182 characters of in extant jawed vertebrates comprises the skull, jaws,
skeletal design as possible design options in morphospace, vertebrae, gills and limb skeletons. Cartilage has an even
that is, as a three-dimensional (3D) representation of the more diverse distribution and a much longer evolutionary
distributionofallknownmorphologies.Ofthese182charac- history than does bone, enamel or dentine2. This
ters,146werealreadyinuseinanimalsoftheBurgessShale is because cartilage and cartilage-like tissues form endo-
fauna 530 mya. Indeed, within 15 million years of the skeletalelementsinmanyinvertebrates.
appearanceofthecrowngroupsofthemajorphylainthefos- Although most invertebrates have noncartilaginous
silrecord,80%ofthedesignelementswerealreadyinuse1. endoskeletons, the diversity of taxa with cartilage is aston-
The four classes recognised by Linnaeus (cid:1) ishing(Chapters3and4).Wherethereisanexoskeletonor
Mammalia, Aves, Amphibia, Pisces (cid:1) were recognised as cuticle in invertebrates (cid:1) and there usually is (cid:1) it is com-
a single group of animals with bone by J. G. C. Barsch in posed of chitin (sometimes with glycoproteins; sometimes
1788, with the names Knochenthiere and Ossea, by Jean- mineralised)orcalciumcarbonate,butnotofcalciumphos-
Baptist Lamarck in 1801 as animaux a` vertebres, and by phate,whichisthemajorcomponentofbone3.Neitherbone
ErnstHaeckelin1866asVertebrates(Nielsen,2012). normineralisedcartilageisfoundininvertebrates,although,
Bone is not the only vertebrate skeletal tissue, however.
Vertebrates have four classesof mineralised tissues: bone,
A. Aunifiedontologyforthevertebrateskeletalsystemisunderdevelop-
cartilage, dentine and enamel. This may seem an unlikely
mentathttp://www.phenoscape.org.Skeletalsystems,tissues,elements,cell
list.Normally,wethinkofcartilageandboneasskeletaltis- typesandskeletogenicprocessesallcanbeaccessedandverifiedonthissite.
sues,andofenamelanddentineasdentaltissuesassociated Forevaluationsofthesite,seeMabeeetal.(2012)andDahduletal.(2013).
BonesandCartilage.DOI:http://dx.doi.org/10.1016/B978-0-12-416678-3.00001-X
©2015ElsevierInc.Allrightsreserved. 3
4 PART | I VertebrateSkeletalTissues
(A) Enamel asdiscussedinChapter4,someinvertebratecartilageshave
surprisinglybone-likefeatures.
Dentine
Mineralisation isnottheexclusivepropertyofthefour
Bone of attachment
vertebrate mineralised tissues. Mineralisation is ubiqui-
Basal bone tous within metazoans and is a property of many single-
celled organisms. Mineralisation can place enormous
Perichondrial bone demands on an organism, for example, when deer annu-
(B)
Endochondral bone ally regrow their antlers (Chapter 8) or when hens lay
Calcified cartilage eggs (Chapter 25). Table 1.2 provides a summary of the
Cartilage
range and diversity of mineralised biological tissues in
various groups and the major organic components associ-
FIGURE1.1 Diagrammaticrepresentationsofthetissuesthatcomprise atedwithmineralisationineach.
(A)thedermal(exo)and(B)theendoskeletonsofvertebrates.Themajor
The innocent phrase ‘the major organic components
differenceisthatthedermalskeletonisbasedondentineandassociated
associated with mineralisation’ hides a mountain of com-
bone, whereas the endoskeletonis based on cartilage. (A) Enamel caps
the dentine in the dermal skeleton. Individual exoskeletal units (odon- plexity. Collagen is a major extracellular molecule asso-
todes),whichproducedentineandboneofattachment,fusetoadjacent ciated with mineralisation in vertebrates, but there are 28
basalbone.(B)Thecartilageoftheendoskeletonmay(i)remainunmi- types of collagen molecules, many associated with more
neralised,(ii) mineralise and remainas a permanent mineralised(calci-
than one of the skeletal tissues. Furthermore, each colla-
fied) cartilage, (iii) be surrounded by perichondrial bone or (iv) be
gen molecule (fibril) is composed of three pro-collagen
invadedandreplacedbyendochondralbone.
chains, which may all be the product of a single collagen
TABLE1.1 SkeletalSystemsandModesofOssificationa
Structure Definition ModeofOssification
Exoskeleton Skeletalsystemthatformsincontactwiththeepithelialectoderm; Intramembranousossification
dermalbone,dermalscales,finrays,gillrakersandteeth
Endoskeleton Skeletalsystemthatdoesnotformincontactwithectoderm; Allossificationtypes
endochondralbone
Endochondralbone Typeofbonethatreplacesapreformedcartilagemodel;themajority Endochondralossification
oftheendoskeleton
Perichondrialbone Bonethatdevelopsfromtheperichondrium Perichondrialossification
Membranebone Typeofbonethatisnotpreformedincartilage Intramembranousossification
Sesamoids,osteoderms Bonesthatdevelopindenseconnectivetissue;normaland Intramembranousossification
pathologicalossifications
Perichordalbone Typeofbonethatformsintheconnectivetissuesheathsurrounding Perichordalossification
thenotochord
Dermalbone Typeofbonethatisnotpreformedincartilageandthatdevelopsin Intramembranousossification
contactwithectoderm;themajorityoftheexoskeleton
aModifiedfromHiltonandBemis(1999)towhichIhaveaddedmodesofossification.
TABLE1.2 TheDiversityofMineralisationofBiologicalTissuesa
Group MineralisedTissues ChemicalFormula MajorOrganicComponents
Plant Cellwall CaCO Cellulose,pectin,lignin
3
Diatoms Exoskeleton Si Pectin
Radiolaria Exoskeleton SrSO (cid:1)
4
Coelenterates,spongesandmolluscs Exoskeleton CaCO Proteins,conchiolin
3
Arthropoda Exoskeleton CaCO Chitin,proteins
3
Vertebrates Exo-andendoskeleton Ca (PO ) OH ,CaCO Collagen,mucopolysaccharides
10 46 2 3
aBasedondatafromDacke(1979).
Chapter | 1 VertebrateSkeletalTissues 5
gene, or the products of three or more collagen genes. Bonematrixispermeatedbycanals(Haversiancanals;
Some of this complexity (cid:1) the major types of collagen in see Chapter 2). Haversian canals contain osteocyte pro-
skeletal tissues, the pro-collagen peptide bases and termi- cesses (canaliculi) connected by gap junctions to other
nology for the genes that produce those peptides (cid:1) is osteocytes,toosteoblastsandtoosteogeniccellsonthesur-
summarisedinTable1.3. facevia gap junctions, forming a syncytium.Thehistology
The four broad classes of vertebrate skeletal tissues of bone, including a short history of its discovery, is out-
may be further subdivided in ways that reflect the inter- lined in Chapter 2. Bone is modelled, remodelled and/or
ests ofindividual skeletal biologists and the scope oftheir removedbymononucleatedormultinucleatedosteoclasts
fields. Embryologists subdivide skeletal tissues according (andsometimesbyosteocytes)byprocessesdiscussedmore
to developmental process, anatomists according to struc- fully in Chapters 2 and 15. Type I collagen, the product of
ture, pathologists based on deviation from the norm and the Col1α1 and Col1α2 (Table 1.3) genes, is the major
soon. extracellularmatrixproteinofbone.Osteocalcin,osteopon-
I add a fifth ‘catch-all’ category to encompass those tin and osteonectin are the major noncollagenous proteins
tissues that, because of one or more criteria, are interme- (Box1.2).
diate between two of the four mineralised tissues found The first bone matrix deposited is unmineralised and
in vertebrates. Examples are tissues intermediate between known as osteoid. Subsequently, osteoid is impregnated
bone and cartilage (chondroid, chondroid bone), between with hydroxyapatite to the mineralised tissue we know as
cartilage and notochord (chordoid), between bone and bone. An organic layer (cid:1) the lamina limitans (cid:1) separates
dentine (osteodentine, cementum) and between enamel osteoidfromalreadymineralisedbone(Scherft,1978).
and dentine (enameloid). The usefulness of this category Bone is an aerobic tissue with high oxygen consump-
for understanding the dynamic development of skeletal tion. Bone functions to support the body and protect
tissueswillbecomeapparentasweproceed. major organs such as the brain and spinal cord and is a
To call these tissues ‘intermediate’ reveals a mamma- site of attachment for ligaments and muscles. Bone is a
lianbias.Thetissuesareintermediatebecausetheydonot storehouse for calcium and phosphorus, and a major site
fitnicelyintoourcategoriesofcartilageandbone,enamel for metabolic regulation of mineral homoeostasis. Bone
or dentine as primarily studied in mammals. Many inver- houses the haematopoietic tissues of adult mammals.
tebrate cartilages fit into a category of ‘intermediate tis- Bone is found only in vertebrates. Extant jawless verte-
sues’ if classified based on vertebrate cartilages (Cole and brates (lampreys), craniates (hagfishes) and all inverte-
Hall, 2004a,b, *2009; *Cole 2011; *Hall and Gillis, brates lack bone. Perhaps surprisingly (see below)
2013), a topic discussed further in Chapter 4. So bear in cartilaginousfisheshavebone.
mind that what we call intermediate tissues in lineages
such as fish are perfectly respectable terminal tissues in
those taxa. The term intermediate is not meant to imply
CARTILAGE
that the tissues are transitional in the sense of not being
permanent. They are intermediate in phenotype and Cartilage is an avascular, supporting and articular skele-
molecular products. They are not intermediate in the tal tissue consisting of cells in an extracellular matrix that
sense of being embryonic or an early stage on the way to may or may not mineralise depending on cartilage type,
transformingintoanothertissue. species or group of organisms; many invertebrates have
cartilage but it never mineralises. Like bone, cartilage can
ariseectopicallyoutsidetheskeleton,forexample,incon-
BONE
nectivetissue,inskeletalmuscle,andintheheart.Indeed,
Bone is a vascularised, supporting skeletal tissue (cid:1) as discussed in Box 17.2, cardiac cartilage is a normal
although bone may also arise ectopically outside the componentoftheskeletoninmanytaxa.
skeleton4(cid:1)consistingofcellsandamineralised extracel- Cartilage is deposited by cartilage-forming cells
lular matrix. Bone is deposited by bone-forming cells (chondroblasts, chondrocytes; Figure 1.7) and removed
(osteoblasts, osteocytes), the majority of which are cili- by mononucleated and multinucleated chondroclasts.
ated (Figure 1.2 and Box 1.1). Osteoblasts cease dividing Cartilage cells are separated from one another by pericel-
when they transform into osteocytes. The fluid content of lular and extracellular matrix. Unlike bone cells, chondro-
boneislow.Embryologically,bonearisesfrommesoderm cytes lack connecting cell processes. As discussed in Box
and from neural crest, which are two of the four germ 1.1 and illustrated in Figure 1.3, some chondrocytes are
layers of vertebrate embryos, the four being ectoderm, ciliated. Most chondrocytes continue to divide throughout
endoderm, mesoderm and neural crest (Chapter 16, and life, although in some cartilages (mammalian articular
see Hall, *1997c, 2000a,b, 2005a, *2009, and J.R. Stone cartilages, for example), the number of dividing cells may
andHall,*2004). belessthan1%ofthechondrocytepopulation.