Wikipedia

Osteoblast

(Redirected fromOsteoprogenitor)

Osteoblasts(from theGreekcombining forms for "bone",ὀστέο-,osteo-and βλαστάνω,blastanō"germinate" ) arecellswith a singlenucleusthat synthesizebone.However, in the process ofbone formation,osteoblasts function in groups of connected cells. Individual cells cannot make bone. A group of organized osteoblasts together with the bone made by a unit of cells is usually called theosteon.

Osteoblast
Osteoblasts(purple) rimming a bony spicule (pink - on diagonal of image). In this routinely fixed and decalcified (bone mineral removed) tissue, the osteoblasts have retracted and are separated from each other and from their underlying matrix. In living bone, the cells are linked bytight junctionsandgap junctions,and integrated with underlying osteocytes and matrixH&E stain.
Illustration showing a single osteoblast
Details
LocationBone
FunctionFormation ofbone tissue
Identifiers
Greekosteoblastus
MeSHD010006
THH2.00.03.7.00002
FMA66780
Anatomical terms of microanatomy

Osteoblasts are specialized, terminally differentiated products ofmesenchymal stem cells.[1]They synthesize dense, crosslinkedcollagenand specialized proteins in much smaller quantities, includingosteocalcinandosteopontin,which compose the organic matrix of bone.

In organized groups of disconnected cells, osteoblasts producehydroxyapatite,thebone mineral,that is deposited in a highly regulated manner, into the inorganic matrix forming a strong and densemineralized tissue,the mineralized matrix. The mineralizedskeletonis the main support for the bodies of air breathingvertebrates.It is also an important store of minerals for physiologicalhomeostasisincluding bothacid-base balanceandcalciumorphosphatemaintenance.[2][3]

Bone structure

edit

Theskeletonis a large organ that isformed and degradedthroughout life in the air-breathing vertebrates. The skeleton, often referred to as the skeletal system, is important both as a supporting structure and for maintenance of calcium, phosphate, andacid-base statusin the whole organism.[4]The functional part of bone, thebone matrix,is entirely extracellular. The bone matrix consists ofproteinandmineral.The protein forms theorganic matrix.It is synthesized and then the mineral is added. The vast majority of the organic matrix iscollagen,which providestensile strength.The matrix is mineralized by deposition of hydroxyapatite (alternative name, hydroxylapatite). This mineral is hard, and providescompressive strength.Thus, the collagen and mineral together are acomposite materialwith excellent tensile and compressive strength, which can bend under a strain and recover its shape without damage. This is calledelastic deformation.Forces that exceed the capacity of bone to behave elastically may cause failure, typicallybone fractures.[citation needed]

Bone remodeling

edit

Bone is a dynamic tissue that is constantly beingreshaped by osteoblasts,which produce and secrete matrix proteins and transport mineral into the matrix, andosteoclasts,which break down the tissues.

Osteoblasts

edit

Osteoblasts are the major cellular component of bone. Osteoblasts arise frommesenchymal stem cells(MSC). MSC give rise to osteoblasts,adipocytes,andmyocytesamong other cell types. Osteoblast quantity is understood to be inversely proportional to that of marrow adipocytes which comprisemarrow adipose tissue (MAT).Osteoblasts are found in large numbers in theperiosteum,the thin connective tissue layer on the outside surface of bones, and in theendosteum.

Normally, almost all of the bone matrix, in the air breathingvertebrates,is mineralized by the osteoblasts. Before the organic matrix is mineralized, it is called theosteoid.Osteoblasts buried in the matrix are calledosteocytes.During bone formation, the surface layer of osteoblasts consists of cuboidal cells, calledactive osteoblasts.When the bone-forming unit is not actively synthesizing bone, the surface osteoblasts are flattened and are calledinactive osteoblasts.Osteocytes remain alive and are connected by cell processes to a surface layer of osteoblasts. Osteocytes have important functions in skeletal maintenance.

Osteoclasts

edit

Osteoclasts are multinucleated cells that derive from hematopoietic progenitors in the bone marrow which also give rise to monocytes in peripheral blood.[5]Osteoclasts break down bone tissue, and along with osteoblasts and osteocytes form the structural components of bone. In the hollow within bones are many other cell types of thebone marrow.Components that are essential for osteoblast bone formation include mesenchymal stem cells (osteoblast precursor) andblood vesselsthat supply oxygen and nutrients for bone formation. Bone is a highly vascular tissue, and active formation of blood vessel cells, also from mesenchymal stem cells, is essential to support the metabolic activity of bone. The balance of bone formation andbone resorptiontends to be negative with age, particularly in post-menopausal women,[6]often leading to a loss of bone serious enough to cause fractures, which is calledosteoporosis.

Osteogenesis

edit

Bone is formed by one of two processes:endochondral ossificationorintramembranous ossification.Endochondral ossification is the process of forming bone from cartilage and this is the usual method. This form ofbone developmentis the more complex form: it follows the formation of a first skeleton ofcartilagemade bychondrocytes,which is then removed and replaced by bone, made by osteoblasts. Intramembranous ossification is the direct ossification ofmesenchymeas happens during the formation of themembrane bonesof the skull and others.[7]

During osteoblastdifferentiation,the developing progenitor cellsexpress the regulatorytranscription factorCbfa1/Runx2.A second required transcription factor isSp7 transcription factor.[8]Osteochondroprogenitor cellsdifferentiate under the influence ofgrowth factors,although isolated mesenchymal stem cells in tissue culture may also form osteoblasts under permissive conditions that includevitamin Cand substrates foralkaline phosphatase,a keyenzymethat provides high concentrations of phosphate at the mineral deposition site.[1]

Bone morphogenetic proteins

edit

Key growth factors in endochondral skeletal differentiation includebone morphogenetic proteins(BMPs) that determine to a major extent where chondrocyte differentiation occurs and where spaces are left between bones. The system of cartilage replacement by bone has a complex regulatory system.BMP2also regulates early skeletal patterning.Transforming growth factor beta(TGF-β), is part of a superfamily of proteins that include BMPs, which possess common signaling elements in theTGF beta signaling pathway.TGF-β is particularly important incartilagedifferentiation, which generally precedes bone formation for endochondral ossification. An additional family of essential regulatory factors is thefibroblast growth factors(FGFs) that determine where skeletal elements occur in relation to the skin

Steroid and protein hormones

edit

Many other regulatory systems are involved in the transition of cartilage to bone and in bone maintenance. A particularly important bone-targeted hormonal regulator isparathyroid hormone(PTH). Parathyroid hormone is a protein made by theparathyroidgland under the control of serum calcium activity.[3]PTH also has important systemic functions, including to keep serum calcium concentrations nearly constant regardless of calcium intake. Increasing dietary calcium results in minor increases in blood calcium. However, this is not a significant mechanism supporting osteoblast bone formation, except in the condition of low dietary calcium; further, abnormally high dietary calcium raises the risk of serious health consequences not directly related to bone mass includingheart attackandstroke.[9]Intermittent PTH stimulation increases osteoblast activity, although PTH is bifunctional and mediates bone matrix degradation at higher concentrations.

The skeleton is also modified for reproduction and in response to nutritional and otherhormonestresses; it responds tosteroids,includingestrogenandglucocorticoids,which are important in reproduction and energy metabolism regulation. Bone turnover involves major expenditures of energy for synthesis and degradation, involving many additional signals includingpituitaryhormones. Two of these areadrenocorticotropic hormone(ACTH)[10]andfollicle stimulating hormone.[11]The physiological role for responses to these, and several otherglycoproteinhormones, is not fully understood, although it is likely that ACTH is bifunctional, like PTH, supporting bone formation with periodic spikes of ACTH, but causing bone destruction in large concentrations. In mice, mutations that reduce the efficiency of ACTH-induced glucocorticoid production in the adrenals cause the skeleton to become dense (osteoscleroticbone).[12][13]

Organization and ultrastructure

edit

In well-preserved bone studied at high magnification viaelectron microscopy,individual osteoblasts are shown to be connected bytight junctions,which preventextracellular fluidpassage and thus create a bone compartment separate from the general extracellular fluid.[14]The osteoblasts are also connected bygap junctions,small pores that connect osteoblasts, allowing the cells in one cohort to function as a unit.[15]The gap junctions also connect deeper layers of cells to the surface layer (osteocyteswhen surrounded by bone). This was demonstrated directly by injecting lowmolecular weightfluorescent dyesinto osteoblasts and showing that the dye diffused to surrounding and deeper cells in the bone-forming unit.[16]Bone is composed of many of these units, which are separated by impermeable zones with no cellular connections, called cement lines.

Collagen and accessory proteins

edit

Almost all of the organic (non-mineral) component of bone is densecollagentype I,[17]which forms dense crosslinked ropes that give bone its tensile strength. By mechanisms still unclear, osteoblasts secrete layers of oriented collagen, with the layers parallel to the long axis of the bone alternating with layers at right angles to the long axis of the bone every fewmicrometers.Defects in collagen type I cause the commonest inherited disorder of bone, calledosteogenesis imperfecta.[18]

Minor, but important, amounts of small proteins, includingosteocalcinandosteopontin,are secreted in bone's organic matrix.[19]Osteocalcin is not expressed at significant concentrations except in bone, and thus osteocalcin is a specific marker for bone matrix synthesis.[20]These proteins link organic and mineral component of bone matrix.[21]The proteins are necessary for maximal matrix strength due to their intermediate localization between mineral and collagen.

However, in mice where expression of osteocalcin or osteopontin was eliminated by targeted disruption of the respective genes (knockout mice), accumulation of mineral was not notably affected, indicating that organization of matrix is not significantly related to mineral transport.[22][23]

Bone versus cartilage

edit

The primitive skeleton iscartilage,a solid avascular (without blood vessels) tissue in which individual cartilage-matrix secreting cells, orchondrocytes,occur. Chondrocytes do not have intercellular connections and are not coordinated in units. Cartilage is composed of a network ofcollagentype II held in tension by water-absorbing proteins, hydrophilicproteoglycans.[24]This is the adult skeleton incartilaginous fishessuch assharks.It develops as the initial skeleton in more advancedclassesof animals.

In air-breathing vertebrates, cartilage is replaced by cellular bone. A transitional tissue is mineralizedcartilage.Cartilage mineralizes by massive expression of phosphate-producing enzymes, which cause high local concentrations of calcium and phosphate that precipitate.[24]This mineralized cartilage is not dense or strong. In the air breathing vertebrates it is used as a scaffold for formation of cellular bone made by osteoblasts, and then it is removed byosteoclasts,which specialize in degrading mineralized tissue.

Osteoblasts produce an advanced type of bone matrix consisting of dense, irregular crystals ofhydroxyapatite,packed around the collagen ropes.[25]This is a strong composite material that allows the skeleton to be shaped mainly as hollow tubes. Reducing the long bones to tubes reduces weight while maintaining strength.

Mineralization of bone

edit

The mechanisms of mineralization are not fully understood. Fluorescent, low-molecular weight compounds such astetracyclineorcalceinbind strongly to bone mineral, when administered for short periods. They then accumulate in narrow bands in the new bone.[26]These bands run across the contiguous group of bone-forming osteoblasts. They occur at a narrow (sub-micrometer) mineralization front. Most bone surfaces express no new bone formation, no tetracycline uptake and no mineral formation. This strongly suggests that facilitated oractive transport,coordinated across the bone-forming group, is involved in bone formation, and that only cell-mediated mineral formation occurs. That is, dietary calcium does not create mineral by mass action.

The mechanism of mineral formation in bone is clearly distinct from thephylogeneticallyolder process by which cartilage is mineralized: tetracycline does not label mineralized cartilage at narrow bands or in specific sites, but diffusely, in keeping with a passive mineralization mechanism.[25]

Osteoblasts separate bone from the extracellular fluid by tight junctions[14]by regulated transport. Unlike in cartilage,phosphateandcalciumcannot move in or out by passive diffusion, because thetight osteoblast junctionsisolate the bone formation space. Calcium is transported across osteoblasts byfacilitated transport(that is, by passive transporters, which do not pump calcium against a gradient).[25]In contrast, phosphate is actively produced by a combination of secretion of phosphate-containing compounds, includingATP,and byphosphatasesthat cleave phosphate to create a high phosphate concentration at the mineralization front.Alkaline phosphataseis a membrane-anchored protein that is a characteristic marker expressed in large amounts at the apical (secretory) face of active osteoblasts.

Major features of the bone-forming complex,the osteon, composed of osteoblasts and osteocytes.

At least one more regulated transport process is involved. Thestoichiometryof bone mineral basically is that ofhydroxyapatiteprecipitating from phosphate, calcium, and water at a slightly alkalinepH:[27]

6 HPO2−4+ 2 H2O + 10 Ca2+⇌ Ca10(PO4)6(OH)2+ 8 H+

In a closed system as mineral precipitates, acid accumulates, rapidly lowering thepHand stopping further precipitation. Cartilage presents no barrier to diffusion and acid therefore diffuses away, allowing precipitation to continue. In the osteon, where matrix is separated from extracellular fluid by tight junctions, this cannot occur. In the controlled, sealed compartment, removing H+drives precipitation under a wide variety of extracellular conditions, as long as calcium and phosphate are available in the matrix compartment.[28]The mechanism by which acid transits the barrier layer remains uncertain. Osteoblasts have capacity for Na+/H+exchange via the redundant Na/H exchangers, NHE1 and NHE6.[29]This H+exchange is a major element in acid removal, although the mechanism by which H+is transported from the matrix space into the barrier osteoblast is not known.

In bone removal, a reverse transport mechanism uses acid delivered to the mineralized matrix to drive hydroxyapatite into solution.[30]

Osteocyte feedback

edit

Feedback from physical activity maintains bone mass, while feedback from osteocytes limits the size of the bone-forming unit.[31][32][33]An important additional mechanism is secretion by osteocytes, buried in the matrix, ofsclerostin,a protein that inhibits a pathway that maintains osteoblast activity. Thus, when the osteon reaches a limiting size, it deactivates bone synthesis.[34]

Morphology and histological staining

edit

Hematoxylin and eosinstaining (H&E) shows that the cytoplasm of active osteoblasts is slightlybasophilicdue to the substantial presence ofrough endoplasmic reticulum.The active osteoblast produces substantial collagen type I. About 10% of the bone matrix is collagen with the balance mineral.[27]The osteoblast's nucleus is spherical and large. An active osteoblast is characterized morphologically by a prominentGolgi apparatusthat appears histologically as a clear zone adjacent to the nucleus. The products of the cell are mostly for transport into the osteoid, the non-mineralized matrix. Active osteoblasts can be labeled by antibodies toType-I collagen,or using naphthol phosphate and thediazoniumdye fast blue to demonstrate alkaline phosphataseenzymeactivity directly.

  • Osteoblast (Wright Giemsa stain, 100x)
  • Light micrographofdecalcifiedcancellous bone displaying osteoblasts actively synthesizing osteoid, containing two osteocytes.
  • Light micrographof undecalcified tissue displaying osteoblasts actively synthesizing osteoid (center).
  • Light micrographof undecalcified tissue displaying osteoblasts actively synthesizing rudimentary bone tissue (center).
  • Osteoblasts lining bone (H&E stain).

Isolation of Osteoblasts

edit
  1. The first isolation technique by microdissection method was originally described by Fell et al.[35]using chick limb bones which were separated into periosteum and remaining parts. She obtained cells which possessed osteogenic characteristics from cultured tissue using chick limb bones which were separated into periosteum and remaining parts. She obtained cells which possessed osteogenic characteristics from cultured tissue.
  2. Enzymatic digestion is one of the most advanced techniques for isolating bone cell populations and obtaining osteoblasts. Peck et al. (1964)[36]described the original method that is now often used by many researchers.
  3. In 1974 Jones et al.[37]found that osteoblasts moved laterally in vivo and in vitro under different experimental conditions and described the migration method in detail. The osteoblasts were, however, contaminated by cells migrating from the vascular openings, which might include endothelial cells and fibroblasts.

See also

edit

References

edit
  1. ^abPittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (April 1999). "Multilineage potential of adult human mesenchymal stem cells".Science.284(5411): 143–7.Bibcode:1999Sci...284..143P.doi:10.1126/science.284.5411.143.PMID10102814.
  2. ^Arnett T (2003)."Regulation of bone cell function by acid-base balance".Proc Nutr Soc.62(2): 511–20.doi:10.1079/pns2003268.PMID14506899.
  3. ^abBlair HC, Zaidi M, Huang CL, Sun L (November 2008). "The developmental basis of skeletal cell differentiation and the molecular basis of major skeletal defects".Biol Rev Camb Philos Soc.83(4): 401–15.doi:10.1111/j.1469-185X.2008.00048.x.PMID18710437.S2CID20459725.
  4. ^Blair HC, Sun L, Kohanski RA (November 2007). "Balanced regulation of proliferation, growth, differentiation, and degradation in skeletal cells".Ann. N. Y. Acad. Sci.1116(1): 165–73.Bibcode:2007NYASA1116..165B.doi:10.1196/annals.1402.029.PMID17646258.S2CID22605157.
  5. ^Loutit, J.F.; Nisbet, N.W. (January 1982). "The Origin of Osteoclasts".Immunobiology.161(3–4): 193–203.doi:10.1016/S0171-2985(82)80074-0.PMID7047369.
  6. ^Nicks KM, Fowler TW, Gaddy D (June 2010). "Reproductive hormones and bone".Curr Osteoporos Rep.8(2): 60–7.doi:10.1007/s11914-010-0014-3.PMID20425612.S2CID43825140.
  7. ^Larsen, William J. (2001).Human embryology(3. ed.). Philadelphia, Pa.: Churchill Livingstone. pp.355–357.ISBN0-443-06583-7.
  8. ^Karsenty G (2008)."Transcriptional control of skeletogenesis".Annu Rev Genom Hum Genet.9:183–96.doi:10.1146/annurev.genom.9.081307.164437.PMID18767962.
  9. ^Reid IR, Bristow SM, Bolland MJ (April 2015). "Cardiovascular complications of calcium supplements".J. Cell. Biochem.116(4): 494–501.doi:10.1002/jcb.25028.PMID25491763.S2CID40654125.
  10. ^Zaidi M, Sun L, Robinson LJ, Tourkova IL, Liu L, Wang Y, Zhu LL, Liu X, Li J, Peng Y, Yang G, Shi X, Levine A, Iqbal J, Yaroslavskiy BB, Isales C, Blair HC (May 2010)."ACTH protects against glucocorticoid-induced osteonecrosis of bone".Proc. Natl. Acad. Sci. U.S.A.107(19): 8782–7.Bibcode:2010PNAS..107.8782Z.doi:10.1073/pnas.0912176107.PMC2889316.PMID20421485.
  11. ^Sun L, Peng Y, Sharrow AC, Iqbal J, Zhang Z, Papachristou DJ, Zaidi S, Zhu LL, Yaroslavskiy BB, Zhou H, Zallone A, Sairam MR, Kumar TR, Bo W, Braun J, Cardoso-Landa L, Schaffler MB, Moonga BS, Blair HC, Zaidi M (April 2006)."FSH directly regulates bone mass".Cell.125(2): 247–60.doi:10.1016/j.cell.2006.01.051.PMID16630814.S2CID7544706.
  12. ^Hoekstra M, Meurs I, Koenders M, Out R, Hildebrand RB, Kruijt JK, Van Eck M, Van Berkel TJ (April 2008)."Absence of HDL cholesteryl ester uptake in mice via SR-BI impairs an adequate adrenal glucocorticoid-mediated stress response to fasting".J. Lipid Res.49(4): 738–45.doi:10.1194/jlr.M700475-JLR200.hdl:2066/69489.PMID18204096.
  13. ^Martineau C, Martin-Falstrault L, Brissette L, Moreau R (January 2014)."The atherogenic Scarb1 null mouse model shows a high bone mass phenotype".Am. J. Physiol. Endocrinol. Metab.306(1): E48–57.doi:10.1152/ajpendo.00421.2013.PMC3920004.PMID24253048.
  14. ^abArana-Chavez VE, Soares AM, Katchburian E (August 1995)."Junctions between early developing osteoblasts of rat calvaria as revealed by freeze-fracture and ultrathin section electron microscopy".Arch. Histol. Cytol.58(3): 285–92.doi:10.1679/aohc.58.285.PMID8527235.
  15. ^Doty SB (1981). "Morphological evidence of gap junctions between bone cells".Calcif. Tissue Int.33(5): 509–12.doi:10.1007/BF02409482.PMID6797704.S2CID29501339.
  16. ^Yellowley CE, Li Z, Zhou Z, Jacobs CR, Donahue HJ (February 2000)."Functional gap junctions between osteocytic and osteoblastic cells".J. Bone Miner. Res.15(2): 209–17.doi:10.1359/jbmr.2000.15.2.209.PMID10703922.S2CID7632980.
  17. ^Reddi AH, Gay R, Gay S, Miller EJ (December 1977)."Transitions in collagen types during matrix-induced cartilage, bone, and bone marrow formation".Proc. Natl. Acad. Sci. U.S.A.74(12): 5589–92.Bibcode:1977PNAS...74.5589R.doi:10.1073/pnas.74.12.5589.PMC431820.PMID271986.
  18. ^Kuivaniemi H, Tromp G, Prockop DJ (April 1991)."Mutations in collagen genes: causes of rare and some common diseases in humans".FASEB J.5(7): 2052–60.doi:10.1096/fasebj.5.7.2010058.PMID2010058.S2CID24461341.
  19. ^Aubin JE, Liu F, Malaval L, Gupta AK (August 1995). "Osteoblast and chondroblast differentiation".Bone.17(2 Suppl): 77S–83S.doi:10.1016/8756-3282(95)00183-E.PMID8579903.
  20. ^Delmas PD, Demiaux B, Malaval L, Chapuy MC, Meunier PJ (April 1986). "[Osteocalcin (or bone gla-protein), a new biological marker for studying bone pathology]".Presse Med(in French).15(14): 643–6.PMID2939433.
  21. ^Roach HI (June 1994). "Why does bone matrix contain non-collagenous proteins? The possible roles of osteocalcin, osteonectin, osteopontin and bone sialoprotein in bone mineralisation and resorption".Cell Biol. Int.18(6): 617–28.doi:10.1006/cbir.1994.1088.PMID8075622.S2CID20913443.
  22. ^Boskey AL, Gadaleta S, Gundberg C, Doty SB, Ducy P, Karsenty G (September 1998)."Fourier transform infrared microspectroscopic analysis of bones of osteocalcin-deficient mice provides insight into the function of osteocalcin".Bone.23(3): 187–96.doi:10.1016/s8756-3282(98)00092-1.PMID9737340.
  23. ^Thurner PJ, Chen CG, Ionova-Martin S, Sun L, Harman A, Porter A, Ager JW, Ritchie RO, Alliston T (June 2010)."Osteopontin deficiency increases bone fragility but preserves bone mass".Bone.46(6): 1564–73.doi:10.1016/j.bone.2010.02.014.PMC2875278.PMID20171304.
  24. ^abBlair HC, Zaidi M, Schlesinger PH (June 2002)."Mechanisms balancing skeletal matrix synthesis and degradation".Biochem. J.364(Pt 2): 329–41.doi:10.1042/BJ20020165.PMC1222578.PMID12023876.
  25. ^abcBlair HC, Robinson LJ, Huang CL, Sun L, Friedman PA, Schlesinger PH, Zaidi M (2011)."Calcium and bone disease".BioFactors.37(3): 159–67.doi:10.1002/biof.143.PMC3608212.PMID21674636.
  26. ^Frost HM (1969). "Tetracycline-based histological analysis of bone remodeling".Calcif Tissue Res.3(1): 211–37.doi:10.1007/BF02058664.PMID4894738.S2CID9373656.
  27. ^abNeuman WF, Neuman MW (1958-01-01).The Chemical Dynamics of Bone Mineral.University of Chicago Press.ISBN0-226-57512-8.[page needed]
  28. ^Schartum S, Nichols G (May 1962)."Concerning pH gradients between the extracellular compartment and fluids bathing the bone mineral surface and their relation to calcium ion distribution".J. Clin. Invest.41(5): 1163–8.doi:10.1172/JCI104569.PMC291024.PMID14498063.
  29. ^Liu L, Schlesinger PH, Slack NM, Friedman PA, Blair HC (June 2011)."High capacity Na+/H+ exchange activity in mineralizing osteoblasts".J. Cell. Physiol.226(6): 1702–12.doi:10.1002/jcp.22501.PMC4458346.PMID21413028.
  30. ^Blair HC, Teitelbaum SL, Ghiselli R, Gluck S (August 1989). "Osteoclastic bone resorption by a polarized vacuolar proton pump".Science.245(4920): 855–7.Bibcode:1989Sci...245..855B.doi:10.1126/science.2528207.PMID2528207.
  31. ^Klein-Nulend J, Nijweide PJ, Burger EH (June 2003). "Osteocyte and bone structure".Curr Osteoporos Rep.1(1): 5–10.doi:10.1007/s11914-003-0002-y.PMID16036059.S2CID9456704.
  32. ^Dance, Amber (23 February 2022)."Fun facts about bones: More than just scaffolding".Knowable Magazine.doi:10.1146/knowable-022222-1.Retrieved8 March2022.
  33. ^Robling, Alexander G.; Bonewald, Lynda F. (10 February 2020)."The Osteocyte: New Insights".Annual Review of Physiology.82(1): 485–506.doi:10.1146/annurev-physiol-021119-034332.hdl:1805/30982.ISSN0066-4278.PMC8274561.PMID32040934.Retrieved8 March2022.
  34. ^Baron, Roland; Rawadi, Georges; Roman-Roman, Sergio (2006). "WNT Signaling: A Key Regulator of Bone Mass".Current Topics in Developmental Biology.Vol. 76. pp. 103–127.doi:10.1016/S0070-2153(06)76004-5.ISBN978-0-12-153176-8.PMID17118265.
  35. ^Fell, HB (January 1932)."The Osteogenic Capacity in vitro of Periosteum and Endosteum Isolated from the Limb Skeleton of Fowl Embryos and Young Chicks".Journal of Anatomy.66(Pt 2): 157–180.11.PMC1248877.PMID17104365.
  36. ^Peck, W. A.; Birge, S. J.; Fedak, S. A. (11 December 1964). "Bone Cells: Biochemical and Biological Studies after Enzymatic Isolation".Science.146(3650): 1476–1477.Bibcode:1964Sci...146.1476P.doi:10.1126/science.146.3650.1476.PMID14208576.S2CID26903706.
  37. ^Jones, S.J.; Boyde, A. (December 1977). "Some morphological observations on osteoclasts".Cell and Tissue Research.185(3): 387–97.doi:10.1007/bf00220298.PMID597853.S2CID26078285.

Further reading

edit
edit
Retrieved from "https://en.wikipedia.org/w/index.php?title=Osteoblast&oldid=1251857250#Osteogenesis"