Osteonectin: Function & Diseases

Osteonectin is a protein that plays a significant role in bone mineralization and in this way is involved in the strengthening of bones and teeth. Numerous scientific studies can be found under its synonymous name SPARC, which additionally indicate a link between the release of SPARC and the prognosis of various cancers.

What is osteonectin?

Osteonectin is a protein with a molecular mass of 35 to 45 kilo Daltons (kD). Its mean molecular mass of 40 kD and its localization in the basement membrane led to another name: BM 40 (Basement Membrane Protein 40). Finally, another protein, named Secreted Protein, acidic, Cysteine-rich, or SPARC, was shown to be the same protein. This name indicates different properties: The acidic protein is secreted and is rich in the sulfur-containing amino acid cysteine. Today, the names SPARC and osteonectin are primarily used. Osteonectin is a glycoprotein, meaning that it contains carbohydrate groups (sugar building blocks) in addition to the protein component, and is capable of binding calcium.

Function, action and tasks

Osteonectin acts in the human organism primarily at the cellular level. Thus, as a calcium-binding glycoprotein in bone metabolism, it performs tasks in mineralization. It has a high affinity for hydroxyapatite (a hydroxylated calcium phosphate salt) and is able to bind collagen, a typical structural protein. Mineralization is an important process in which calcium phosphates are incorporated into the organic matrix of body tissues. As a result, these acquire a particular strength. These tissues include bones, cartilage and teeth. Tooth enamel, for example, consists of almost 100 percent hydroxyapatite and is the hardest substance in the human body. In natural tissues, cells are found in a structure called the extracellular matrix. Within this cellular structure, various interactions occur, for which osteonectin also plays a role. Other functions involve cell growth and proliferation (cell proliferation, Latin: proles, sprout; ferre, to bear), which can be modulated in its presence, that is, altered under different conditions. In addition, the protein supports the attachment of cells, a process of great importance for wound healing, as well as the proliferation of certain cell types. Osteonectin participates in bone metabolism, wound healing, and during the regeneration process.

Formation, occurrence, properties, and optimal values

Particularly large amounts of osteonectin are found in immature bone tissues. Specialized bone cells responsible for synthesizing the bone matrix are called osteoblasts. Active osteoblasts contain large amounts of osteonectin, as do cartilage cells and cells that play a role in tooth development (odontoblasts). Furthermore, it is synthesized by fibroblasts. These cells are found in connective tissue and have great importance for the extracellular matrix and its strength. In addition, macrophages (Greek, makros,large; phagein, to eat) are capable of producing the protein as part of wound healing. Macrophages are white blood cells that have important functions in immune defense. Endothelial cells, which line the inside of blood vessels, also synthesize it. Osteonectin can be detected in many metabolically active cells. This fact is used for selected questions to estimate the current metabolic situation. Determination of the amount of this protein is not routinely done as a laboratory test. For characterization of certain biochemical processes within wound healing, bone metabolism, or platelet activation, quantification of the protein can provide important information.

Diseases and disorders

Disease patterns in which the protein is absent have not been described to date. Diseases that appear to be linked to alterations in the protein include lateral cystocele and chorioangioma. Lateral cystocele (lateral protrusion of the urinary bladder toward the vaginal wall) is a connective tissue weakness that can lead to urinary incontinence or retention.A chorioangioma is a rare, benign tumor of the placenta.Far more significant is its influence on processes within cancer development. Due to its diverse properties, the effect on different types of cancer does not seem to be identical. Thus, protein levels differ in different types of cancer. Ovarian, prostate and pancreatic cancers show low levels, while breast cancer, gliomas and melanomas are accompanied by higher levels. It is noteworthy that improvement seems to occur when exercise and sport can increase the level. Exercise showed positive effects in cancer patients. This fact has led to a rethinking of cancer care and the slogan “outrun cancer”. Physical activity seems to influence gene functions. Existing genes can be switched on or off or activated. One possible mechanism probably involves “Secreted protein acidic and rich in cysteine (SPARC)”. This protein is released during physical training. The nature of its influence on cancer growth and spread is currently the subject of controversial debate. There is agreement on the involvement of osteonectin in changes in cancer cell activity and in the tumor environment. In some tumor types, tumor cells show low levels of the protein, while in neighboring cells it is very high. Some studies favor osteonectin as a tumor suppressor in various cancers. In others, the effect appears to be in the opposite direction. One reason may be the simultaneous effect on other molecules and processes, which ultimately influence biological behavior in different ways.