| Chondroblast | |
|---|---|
 Diagram of chondroblasts | |
| Details | |
| Identifiers | |
| Latin | chondroblastus |
| TH | H2.00.03.5.00002 |
| FMA | 66783 |
| Anatomical terms of microanatomy | |
Chondroblasts, orperichondrial cells, is the name given tomesenchymalprogenitor cells in situ which, fromendochondral ossification, will formchondrocytes in the growingcartilagematrix. Another name for them is subchondral cortico-spongious progenitors.[1] They have euchromatic nuclei and stain by basic dyes.
These cells are extremely important inchondrogenesis due to their role in forming both the chondrocytes and cartilage matrix which will eventually form cartilage. Use of the term is technically inaccurate since mesenchymal progenitors can also technically differentiate intoosteoblasts orfat. Chondroblasts are called chondrocytes when they embed themselves in the cartilage matrix, consisting ofproteoglycan andcollagenfibers, until they lie in the matrixlacunae. Once they embed themselves into the cartilage matrix, they grow the cartilage matrix by growing more cartilageextracellular matrix rather than by dividing further.[citation needed]
Within adults and developing adults, most chondroblasts are located in the perichondrium. This is a thin layer of connective tissue which protects cartilage and is where chondroblasts help to expand cartilage size whenever prompted to byhormones such asGH,TH, andglycosaminoglycans.[2] They are located on theperichondrium because the perichondrium, located on the outside of developing bone, is not as heavily ensheathed in cartilage extracellular matrix as the interior and because herecapillaries are located. The type of growth maintained by chondroblasts is calledappositional bone growth and increases the birth of the affected tissue. Perichondrium, and thus chondroblasts, are not found on thearticular cartilage surfaces ofjoints.[citation needed][original research?]
The extracellular matrix secreted by chondroblasts is composed offibers,collagen,hyaluronic acid,proteoglycans,glycoproteins,water, and a host ofmacromolecules. Within finished cartilage, collagen fibers compose 10-20% of the volume, water 65-80%, and the proteoglycan-hyaluronic acid aggregates the remaining portion. Due to the proliferative nature of chondroblasts, cells compose a larger portion of the composition than what is normally found within completed cartilage.[3]
Collagen Type II fibers are responsible for giving the future cartilage matrix itstensile strength. The structure of these fibers, like the majority of collagen fibers, forms a triple helix structure.[3]
Proteoglycans resist the compression generally put upon cartilage and generate the swellingpressure responsible for stress shielding the matrix from compression loading. They attach themselves to up to 100Chondroitin sulfate molecules and up to 50 keratan sulfateglycoaminoglycan chains. These chains together are attached to a hyaluronic acid backbone which, in conjunction with the collagen fibrils, create an interstitial intrafibrillar space in which water is held in by the negative charge of the proteoglycans.[4]
As suggested in the name, mesenchymal progenitors originate from themesoderm. Thesecells, when forming from the mesoderm, specifically form fromembryonic stem cells viainduction throughBMP4 andfibroblast growth factor FGF2 while thefetus is inside the womb. It has been suggested that differentiating embryonic stem cells with these growth factors could prevent stem cells, once injected into potentialpatients, from formingteratomas, or stem cell causedtumors.[5]
An importantgenetic component of this process is Sox9, a HMG boxtranscription factor, which marks progenitor cells for chondrogenic differentiation. Inactivation of the Sox9 gene will result in the loss of all Cartilage, and thus Chondroblast, formation. This factor is also expressed alongside Sox5 and Sox6.[1]
Runx2 is another important genetic component of Chondroblast formation. It has been found that expressing this gene will result in the suppression of the differentiation of chondroblasts. Expression of this gene will also prompt already formed cartilage to undergoendochondral ossification which will prompt the cartilage to form bone.[citation needed]
Thesegenes are not the only factors which determine whether chondroblasts will form. General inactivation or activation of these gene doesn't turn all affected cells into one type or another. Extrinsicenvironmental factors act upstream in determining what cell type will form out of any particular mesenchymal progenitor cell.[citation needed]
Wnt14 is controlled by Col2a1 and is put through the β-Catenin mediatedWnt pathway. Higher levels of Wnt14 prevented chondrocyte differentiation whereas lower levels appeared to allow it. If the Wnt/ β-Catenin pathway is upregulated, then endochondral ossification is encouraged which promotes ossification of the formed cartilage. This pathway is a canonical Wnt pathway because of the β-Catenin that accumulates once Wnt14 signalling is initiated. After Wnt14 is initiated,phosphorylation of the β-Catenin that would normally mark the protein for destruction is suppressed which allows it to accumulate and eventually go into thecell nucleus to bind to the LEF/TCF transcription factors which lead both to the destruction of any remaining phosphorylated β-Catenin as well as the differentiation of mesenchymal progenitor cells intoosteoblasts.[6]
Testing of this pathway has indicated that the Wnt/β-Catenin increasesβ-Catenin levels before the activation of the Runx2 and Osx transcription factors which seems to suggest that early β-Catenin levels can be a sign of whether an early mesenchymal progenitor cell will progress to a chondrocyte or to an osteoblast.[7]
Retinoic acid, part of a family of molecules calledretinoids, need to be repressed in order for Chondroblasts to form. A 2003 study usingtransgenicmice with a weak, constitutively active retinoic acidreceptor found that retinoids maintain cells within condensations in a prechondrogenic, mesenchymal cell state which prevents cell differentiation.[8] It has also been suggested that the inhibition of receptor mediated retinoid signaling inducesSox9 expression which is considered a “master switch” for the differentiation of chondroblasts.[8]
Differentiation of chondroblasts is favored in an environment with high compressiveforce and low partialoxygenpressure which combine to inhibit protein 3, a protein which inhibits cartilage differentiation. These preferences are important since mature cartilagetissue isavascular and thus would be ill-suited to a high oxygen environment.[1]
Chondroblasts appear to migrate to cartilage whenever chondrocytes are destroyed via mechanical force. Remaining chondrocytes divide in order to form more chondroblasts. HMGB-1, a growth factor which promotes chondrocyte division while receptors for advanced glycation products (RAGE) mediatedchemotaxis to clean up cell debris resulting from the damage. Chondroblasts then secrete cartilage matrix around themselves in order to reform the lost cartilage tissue.[citation needed]
However, regeneration is still too slow for patient care to effectively rely on this mechanism of repair. Part of this inability to regenerate quickly from injury results from the relativeavascularnature of cartilage as compared to otherconnective tissues of thehuman body.[citation needed]
Chondroblastomas can sometimes form, which arebenign tumors that form at the sites of endochondral ossification due to over stimulation of the chondroblasts. When they form, they are usually found on the upper or lowertibia as well as the upperhumerus where chondroblast activity is most apparent. Rarely, they can be found on the feet, hands, flat bones, or spine. 30–50% of thesesarcomas have an accompanyingosteoblastoma which is similarly benign.[9]
Chondrosarcoma is a moremalignant type of tumor, but most are low grade tumors and often appear in theaxial skeletal region. It constitutes 20% of skeletal system tumors in theUnited States.[10]