Endocrine Abstracts

Osteocytes make up over 90-95% of bone cells in the adult skeleton making their total cellular mass greater than the mass of the brain. These cells can exist for decades in the bone matrix, much longer than osteoblasts or osteoclasts. In addition to being mechanosensory cells, osteocytes are also secretory cells, releasing sclerostin that inhibits osteoblastic bone formation and producing Rankl, the major activator of osteoclasts. Mechanical loading reduces both sclerostin and Rankl expression, while simultaneously stimulating the release of positive regulators of bone formation such as prostaglandin E2, ATP, and nitric oxide. In addition to these autocrine factors, osteocytes produce paracrine factors such as fibroblast growth factor 23, which targets the kidney to regulate phosphate metabolism. Interestingly, neutralizing antibodies to sclerostin, Rankl, and FGF23, approved as therapeutics, are all osteocyte factors. Parathyroid hormone, PTH, or PTH related protein target osteocytes through the PTH type 1 receptor, highly expressed in osteocytes, to regulate calcium. The osteocyte then reduces the pH within its lacunae and generate enzymes that degrade matrix such as Cathepsin K, Trap, and MMPs to release calcium into the circulation. The major difference between male and female osteocytes is the elevated expression of these genes in females suggesting that osteocytes may be responsible for some of the sex differences in male compared to female bone. As these cells age, they lose their connectivity of their dendritic processes. In the aged skeleton, not only are senescent cells present, but also empty lacunae where previous cells existed. These changes in osteocytes may be the explanation for skeletal resistance to exercise with aging. New functions of osteocytes are being discovered such as conversion into inflammatory cells, in regulating adipogenesis, myogenesis and muscle function, potential crosstalk with the brain, and the role of osteocytes in various forms of cancer.