Cell of The Month: Osteoblasts
Osteoblasts, often referred to as bone-forming cells, are specialized and terminally differentiated products of mesenchymal stem cells whose major function is to synthesize bone in a process known as osteogenesis.
During osteogenesis, osteoblasts are organized into closely packed sheets of connected cells on the bone surface, from which cellular processes may extend through the developing bone. Osteoblasts produce and release proteins, hormones, and other materials into their extracellular environment, where they assemble to form a thin layer (approximately 10 µm thick) of flexible bone tissue called an osteoid (also known as the un-mineralized bone matrix) on the surface of a newly developing bone or a bone that is undergoing repair.
Within the osteoid is an abundance of cross-linked Type I collagen fibers, which make up about 95 % of the bone’s organic matrix and ensure bone flexibility. These collagen fibers are used as the framework for subsequent bone formation. The osteoid becomes mineralized when osteoblasts synthesize an inorganic mineral rich in calcium phosphate called hydroxylapatite, which is deposited in a highly regulated fashion into the un-mineralized matrix to form a strong and dense mineralized tissue known as the mineralized bone matrix.
The bone matrix makes up about one third of the bone, and the remaining two thirds are comprised of salts. Calcium and phosphate ions are the predominant salts found in the non-matrix parts of bone, and these ensure bone rigidity. High concentrations of phosphate at the mineral deposition site are provided via the activity of the enzyme alkaline phosphatase, which is an early marker of osteoblast differentiation and whose expression levels increase upon the progressive differentiation of osteoblasts.
As the osteoblasts repeatedly produce bone matrix and the matrix mineralizes, the osteoblasts become surrounded by the mineralized matrix, eventually becoming buried within the bone, where they become known as osteocytes. As each new layer of bone is formed, the bone becomes stronger and thicker, allowing it to carry out its crucial skeletal support function. Besides skeletal support, the bone mineralization process itself is important for human homeostasis, for example, by regulating the acid-base balance or for calcium homeostasis.
Osteoblasts produce a number of specialized proteins including hormones such as osteocalcin and prostaglandins, which play roles in the regulation of insulin secretion and bone formation, respectively.
Bone Remodeling and Adaptation
Besides de novo bone formation, osteoblasts also play a central role in bone remodeling. During this dynamic process, mature bone tissue is removed from the skeleton (in a process known as bone resorption) by another bone cell type known as osteoclasts, and new bone tissue is formed in its place by osteoblasts. This process is finely balanced, and imbalances between the rate of bone resorption and bone formation can lead to a number of bone diseases, for example, osteoporosis.
Besides helping the skeleton to cope with normal bone aging, bone remodeling also controls bone reshaping or replacement following bone fractures as well as regular wear and tear that occurs during normal physical activity. Bone remodeling also responds to the changing mechanical demands (mechanical loading) of bone. When mechanical loading increases, bone mass increases and vice versa.
Osteoblasts in Research and Medicine
With an aging world population and individuals with complex medical needs living decades longer than before, e.g., those with complex fractures and age-related bone disorders, the demand for novel bone therapies is expected to increase significantly. According to one source, the global orthopedics market is expected to grow by a staggering 25 % from $52.8bn (2017) to $66.2bn as early as 2023, driven primarily by increases in the prevalence of age-related bone disorders such as osteoporosis and large-joint replacements involving the hips and knees. About 7.2 million Americans are currently living with hip or knee replacements, and about 1 million of these surgeries are performed annually in the U.S alone.
Building on successes in large joint replacements, future growth in this area is expected to occur in the number of smaller joint implants e.g., shoulders, wrists, and ankles. Besides bone grafting, transplantation, and the use of artificial implants, the therapeutic delivery of growth factors, cells, serum and proteins, which are collectively known as orthobiologics, has now made its way into modern orthopedic surgical practice.
With ethical considerations surrounding gene- and stem cell therapy, and vascularization challenges associated with the latter, the orthobiologics approach to advance the most as of yet is likely bone-inducing protein therapy. Bone morphogenetic proteins (BMPs) are a family of proteins that induce bone formation, several of which play pivotal roles in osteoblast differentiation. Although controversy exists surrounding its safety, a recombinant form of human BMP2 is now used clinically for a range of bone indications following initial FDA approval in 2002.
As mentioned above, any imbalance between bone formation and resorption may lead to bone loss or excessive bone formation and defects in skeletal integrity. While anti-resorptive drugs to reduce excess bone resorption are available, the treatment of disorders marked by excess or disordered bone formation, for example bone tumors, is much more challenging because of the limited number of safe and effective drugs available to modulate osteoblast numbers and activity. A greater understanding of the complex processes underlying osteoblast function and regulation would contribute to improvements this therapeutic area, possibly leading to cellular therapies based on stem-derived osteoblasts in the future.
For researchers working on any aspect of osteoblast biology and scientists working on preclinical drug development projects related to bone formation and related disorders, the newly launched Tempo-iOsteo™ cells serve as an ideal model system to examine osteoblast function in bone mineralization, matrix formation for skeletal systems, bone remodeling, and bone metabolism. These iPS-derived cells are patient-relevant and can also readily be incorporated into research programs aimed at unraveling the molecular mechanisms underlying bone- and associated disorders such as bone loss, osteoporosis, osteoclast inhibition, and rheumatoid arthritis, to name a few. For those working on biological events that lie upstream of osteoblast differentiation, Tempo-iMSC™: Human iPS-derived Mesenchymal Stem Cells are a popular choice. Uniquely, these cells grow as a monolayer, providing increased flexibility and practicality for screening and high-throughput experiments.
To hear more about Tempo’s offerings related to osteoblasts, don’t hesitate to get in touch with us here.
In the meantime, we would love to know what you are up to with osteoblasts. Feel free to drop us a line via email!
Article by Karen O’Hanlon Cohrt PhD. Contact Karen at firstname.lastname@example.org.
Karen O’Hanlon Cohrt is a Science Writer with a PhD in biotechnology from Maynooth University, Ireland (2011). After her PhD, Karen moved to Denmark and held postdoctoral positions in mycology and later in human cell cycle regulation, before moving to the world of drug discovery. Her broad research background provides the technical know-how to support scientists in diverse areas, and this in combination with her passion for writing helps her to keep abreast of exciting research developments as they unfold. Follow Karen on Twitter @KarenOHCohrt. Karen has been a science writer since 2014; you can find her other work on her portfolio.