Chondroblast

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 by hormones such as GH, TH, and glycosaminoglycans. They are located on the perichondrium because the perichondrium, located on the outside of developing bone, is not as heavily ensheathed in cartilage extracellular matrix as the interior and because here capillaries are located. The type of growth maintained by chondroblasts is called appositional bone growth and increases the girth of the affected tissue. Perichondrium, and thus chondroblasts, are not found on the articular cartilage surfaces of joints. Matrix formation and composition The extracellular matrix secreted by chondroblasts is composed of fibers, collagen, hyaluronic acid, proteoglycans, glycoproteins, water, and a host of macromolecules. 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. Collagen Type II fibers are responsible for giving the future cartilage matrix its tensile strength. The structure of these fibers, like the majority of collagen fibers, forms a triple helix structure. ==Development==

As suggested in the name, mesenchymal progenitors originate from the mesoderm. These cells, when forming from the mesoderm, specifically form from embryonic stem cells via induction through BMP4 and fibroblast growth factor FGF2 while the fetus is inside the womb. It has been suggested that differentiating embryonic stem cells with these growth factors could prevent stem cells, once injected into potential patients, from forming teratomas, or stem cell caused tumors. Signaling, transcription and environmental factors responsible for chondroblast creation Transcription factors An important genetic component of this process is Sox9, a HMG box transcription 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. Testing of this pathway has indicated that the Wnt/β-Catenin increases β-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. Retinoic acid Retinoic acid, part of a family of molecules called retinoids, need to be repressed in order for Chondroblasts to form. A 2003 study using transgenic mice with a weak, constitutively active retinoic acid receptor found that retinoids maintain cells within condensations in a prechondrogenic, mesenchymal cell state which prevents cell differentiation. It has also been suggested that the inhibition of receptor mediated retinoid signaling induces Sox9 expression which is considered a “master switch” for the differentiation of chondroblasts. Environmental factors Differentiation of chondroblasts is favored in an environment with high compressive force and low partial oxygen pressure which combine to inhibit protein 3, a protein which inhibits cartilage differentiation. These preferences are important since mature cartilage tissue is avascular and thus would be ill-suited to a high oxygen environment. ==Function==

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) mediated chemotaxis to clean up cell debris resulting from the damage. Chondroblasts then secrete cartilage matrix around themselves in order to reform the lost cartilage tissue. 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 relative avascular nature of cartilage as compared to other connective tissues of the human body. ==Pathology==

Chondroblastomas can sometimes form, which are benign 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 lower tibia as well as the upper humerus where chondroblast activity is most apparent. Rarely, they can be found on the feet, hands, flat bones, or spine. 30–50% of these sarcomas have an accompanying osteoblastoma which is similarly benign. Chondrosarcoma is a more malignant type of tumor, but most are low grade tumors and often appear in the axial skeletal region. It constitutes 20% of skeletal system tumors in the United States. == See also ==